Type 1 diabetes mellitus results from the autoimmune and inflammatory destruction of insulin-producing islet β cells, rendering individuals devoid of insulin production. Recent studies suggest that combination therap...Type 1 diabetes mellitus results from the autoimmune and inflammatory destruction of insulin-producing islet β cells, rendering individuals devoid of insulin production. Recent studies suggest that combination therapies consisting of anti-inflammatory agents and islet growth-promoting factors have the potential to cause sustained recovery of β cell mass, leading to amelioration or reversal of type 1 diabetes in mouse models. In this study, we hypothesized that the combination of the anti-inflammatory agent lisofylline (LSF) with an active peptide fragment of islet neogenesis associated protein (INGAP peptide) would lead to remission of type 1 diabetes in the non-obese diabetic (NOD) mouse. We treated groups of spontaneously diabetic NOD mice with combinations of LSF, INGAP peptide, or control saline parenterally for up to 6 weeks. Our results demonstrate that the mice receiving combined treatment with LSF and INGAP peptide exhibited partial remission of diabetes with increased plasma insulin levels. Histologic assessment of pancreata in mice receiving combined therapy revealed the presence of islet insulin staining, increased β cell replication, and evidence of Pdx1-positivity in ductal cells. By contrast, diabetic animals showed severe insulitis with no detectible insulin or Pdx1 staining. We conclude that the novel combination treatment with LSF and INGAP peptide has the potential to ameliorate hyperglycemia in the setting of established type 1 diabetes via the recovery of endogenous β cells and warrant further studies.展开更多
The relationships between five classes of Japanese people （i.e., 96 centenarians, 96 Alzheimer＇s disease （AD） patients, 96 Parkinson＇s disease （PD） patients, 96 type 2 diabetic （T2D） patients, and 96 healthy ...The relationships between five classes of Japanese people （i.e., 96 centenarians, 96 Alzheimer＇s disease （AD） patients, 96 Parkinson＇s disease （PD） patients, 96 type 2 diabetic （T2D） patients, and 96 healthy non-obese young males） and their mitochondrial single nucleotide polymorphism （mtSNP） frequencies at individual mtDNA positions of the entire mitochondrial genome were examined using the radial basis function （RBF） network and the modified method. New findings of mitochondrial haplogroups were obtained for individual classes. The five classes of people were associated with the following haplogroups： Japanese centenarians-M7b2, D4b2a, and B5b; Japanese AD patients-G2a, B4cl, and N9b1; Japanese PD patients-M7b2, B4e, and B5b; Japanese T2D patients-B5b, M8al, G, D4, and F1; and Japanese healthy non-obese young males-D4g and D4b1b. From the points of common haplogroups among the five classes, the cente- narians have the common haplogroups M7b2 and B5b with the PD patients and common haplogroup B5b with the T2D patients. In addition, the 112 Japanese semi-supercentenarians （over 105 years old） recently reported were also examined by the method proposed. The results obtained were the haplogroups D4a, B4c1a, M7b2, F1, M1, and B5b. These results are different from the previously reported haplogroup classifications. As the proposed analysis method can predict a person＇s mtSNP constitution and the probabilities of becoming a centenarian, AD patient, PD patient, or T2D patient, it may be useful in initial diagnosis of various diseases.展开更多
BACKGROUND: Triptolide (TPT) is a diterpenoid triepoxide extracted from the Chinese herb Tripterygium wilfordii Hook. F. It exhibits potent immunosuppressive and anti-inflammatory properties. This study was undertaken...BACKGROUND: Triptolide (TPT) is a diterpenoid triepoxide extracted from the Chinese herb Tripterygium wilfordii Hook. F. It exhibits potent immunosuppressive and anti-inflammatory properties. This study was undertaken to investigate its effects on prolongation of islet allograft survival in rodents. Additionally, we investigated whether TPT would be toxic to islet function in vivo. METHODS: We transplanted BALB/c islets to either chemically induced diabetic C57BL/6 mice or spontaneously diabetic non-obese diabetic (NOD) mice. TPT was injected within 2 weeks or continuously, until rejection, in the two combinations. Then, we evaluated the toxicity of TPT on islet function by daily injection to naive BALB/c or diabetic BALB/c that was cured by syngeneic islet transplantation under the kidney capsule. Mice injected with cyclosporine A (CsA) or vehicle served as controls. Intraperitoneal glucose tolerance tests (IPGTTs) performed at 4 and 8 weeks in the naive BALB/c group, and at 2, 4, 6, and 8 weeks in the syngeneic transplanted group. RESULTS: The medium survival time of islets allograft from TPT treated C57BL/6 and NOD recipients were 28.5 days (range 24-30 days, n=10) and 33.0 days (range 15-47 days, n=6), respectively, and they were significantly different from those of the vehicle treated controls, which were 14.0 days (range 13-16 days, n=6) and 5.0 days (range 4-10 days, n=6), respectively (all P<0.0001). The IPGTT demonstrated that there was no difference between the TPT treated and vehicle treated groups, either in the normal or syngeneic transplanted islet BALB/c mice. However, CsA injection impaired islet function in both normal and syngeneic transplanted mice as early as 4 weeks. CONCLUSION: TPT prolonged islets allograft survival in a chemically induced diabetic or an autoimmune diabetic murine model without impairment of islet function. (Hepatobiliary Pancreat Dis Int 2010; 9: 312-318)展开更多
Aim To study the effects of binuclear copper （Ⅱ） threonine complex （Cu2 （Thr）4） as analogue of superoxide dismutase （SOD） on blood glucose, blood lipids and vessels of hearts and kidneys in diabetic mice. Met...Aim To study the effects of binuclear copper （Ⅱ） threonine complex （Cu2 （Thr）4） as analogue of superoxide dismutase （SOD） on blood glucose, blood lipids and vessels of hearts and kidneys in diabetic mice. Methods Diabetic mouse model was established by intraperitioneal injection of alloxan. Low, middle, and high doses of Cu2（Thr）4 at 0.002%, 0.02% and 0.1% were given respectively to diabetic mice following lavage. The fasting blood glucose was determined after the diabetic mice were given Cu2 （Thr）4 for 0, 30, and 45 d. The diabetic mice were killed on the 45th day. Then glycosylated hemoglobin （HbAlc） and blood lipids were assayed, and pathologic changes in hearts and kidneys stained with HE were observed. Results Compared with the control group in which the diabetic mice were given distilled water, the value of blood glucose reduced significantly in middle dose group （P 〈 0.01 ）, followed by that in low dose group （P 〈 0.05）. TC level reduced markedly and HDL level increased significantly in all three treatment groups （P 〈 0.05）. Especially in middle dose group, cardiac muscle fibers were neatly arranged, nucleus and cytoplasm well distributed, glomeruli showing normal structure, cells well distributed and staining being normal. Conclusion Cu2 （Thr）4 reduces blood glucose, regulates blood lipids, and play protective action on the vessels of hearts and kidneys in diabetic mice. The effects of it in middle dose were better than those of other doses.展开更多
The leaves of Aquilaria sinensis（Lour.） Gilg have been used in folk medicine for the treatment of diabetes in Guangdong Province,China.In this study,effects of ethanol extract of Aquilaria sinensis leaves on hypergl...The leaves of Aquilaria sinensis（Lour.） Gilg have been used in folk medicine for the treatment of diabetes in Guangdong Province,China.In this study,effects of ethanol extract of Aquilaria sinensis leaves on hyperglycemia were investigated in diabetic db/db mice.After 4 weeks of administration,the 95%ethanol（EtOH） extract of Aquilaria sinensis leaves （AE）,especially at high dose level（600 mg/kg）,activated AMP-activated protein kinase（AMPK）,resulting in reduced fasting blood glucose and glycosylated hemoglobin levels in db/db mice.In addition,the oral glucose tolerance test（OGTT test） showed that AE could remarkably improve insulin resistance.Compared to Thiazolinediones（TZDs）,no weight gain was observed after AE administration,which is a severe side effect of TZDs.The data suggested that AE could act as an activator of AMPK,and might be used as an alternative to TZDs in the management of obesity-related diabetes.展开更多
Diabetes mellitus(DM)is known to cause reproductive impairment.In men,it has been linked to altered sperm quality and testicular damage.Oxidative stress(OS)plays a pivotal role in the development of DM complications.G...Diabetes mellitus(DM)is known to cause reproductive impairment.In men,it has been linked to altered sperm quality and testicular damage.Oxidative stress(OS)plays a pivotal role in the development of DM complications.Glutathione(GSH)is a part of a nonenzymatic antioxidant defense system that protects lipid,protein,and nucleic acids from oxidative damage.However,the protective effects of exogenous GSH on the male reproductive system have not been comprehensively examined.This study determined the impact of GSH supplementation in ameliorating the adverse effect of type 1 DM on sperm quality and the seminiferous tubules of diabetic C57BL/6NTac mice.GSH at the doses of 15 mg kg^(-1)and 30 mg kg^(-1)was given intraperitoneally to mice weekly for 6 consecutive weeks.The mice were then weighed,euthanized,and had their reproductive organs excised.The diabetic(D Group)showed significant impairment of sperm quality and testicular histology compared with the nondiabetic(ND Group).Diameters of the seminiferous lumen in diabetic mice treated with 15 mg kg^(-1) GSH(DGSH15)were decreased compared with the D Group.Sperm motility was also significantly increased in the DGSH15 Group.Improvement in testicular morphology might be an early indication of the protective roles played by the exogenous GSH in protecting sperm quality from effects of untreated type 1 DM or diabetic complications.Further investigation using different doses and different routes of GSH is necessary to confirm this suggestion.展开更多
AIM:To investigate the potential therapeutic significance of ghrelin and growth hormone releasing peptide 6 (GHRP-6) in diabetic mice with gastric motility disorders. METHODS: A diabetic mouse model was established by...AIM:To investigate the potential therapeutic significance of ghrelin and growth hormone releasing peptide 6 (GHRP-6) in diabetic mice with gastric motility disorders. METHODS: A diabetic mouse model was established by intraperitoneal (ip) injection of alloxan. Diabetic mice were injected ip with ghrelin or GHRP-6 (20-200 μg/kg), and the effects on gastric emptying were measured after intragastric application of phenol red. The effect of atropine, NG-nitro-L-arginine methyl ester hydrochloride (L-NAME) or D-Lys3-GHRP-6 (a growth hormone secretagogue receptor (GHS-R) antagonist) on the gastroprokinetic effect of ghrelin or GHRP-6 (100 μg/kg) was also investigated. The effects of ghrelin or GHRP-6 (0.01-10 μmol/L) on spontaneous or carbachol-induced contractile amplitude were also investigated in vitro, in gastric fundic circular strips taken from diabetic mice. The presence of growth hormone secretagogue receptor 1a transcripts in the fundic strips of diabetic mice was detected by reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: We established a diabetic mouse model with delayed gastric emptying. Ghrelin and GHRP-6 accelerated gastric emptying in diabetic mice with gastroparesis. In the presence of atropine or L-NAME, which delayed gastric emptying, ghrelin and GHRP-6 (100 μg/kg) failed to accelerate gastric emptying. D-Lys3-GHRP-6 also delayed gastric emptying induced by the GHS-R agonist. Ghrelin and GHRP-6 increased the carbachol-induced contractile amplitude in gastric fundicstrips taken from diabetic mice. RT-PCR confirmed the presence of GHS-R mRNA in the strip preparations. CONCLUSION: Ghrelin and GHRP-6 increase gastric emptying in diabetic mice with gastroparesis, perhaps by activating peripheral cholinergic pathways in the enteric nervous system.展开更多
AIM： To investigate the role of O-GIcNAcylation of nuclear factor-kappa B （NF-KB） in retinal ganglion cell （RGC） death and analysedthe effect of Aralia elata （AE） on neurodegen- eration in diabetic mice. METH...AIM： To investigate the role of O-GIcNAcylation of nuclear factor-kappa B （NF-KB） in retinal ganglion cell （RGC） death and analysedthe effect of Aralia elata （AE） on neurodegen- eration in diabetic mice. METHODS： C57BL/6mice with streptozotocin-induced diabetes were fed daily with AE extract or control （CTL） diet at the onset of diabetes mellitus （DM）. Two months af- tar injection of streptozotocin or saline, the degree of cell death and the expression of O-GIcNAc transferase （OGT）, N-acetyl-b-D-glucosaminidase （OGA）, O-GIcNAcylated pro- teins, and O-GIcNAcylation of NF-KB were examined. RESULTS： AE did not affect the metabolic status of diabetic mice. The decrease in the inner retinal thickness （P〈0.001 vs CTL, P〈0.01 vs DM） and increases in RGCs with terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling （P〈0.001 vs CTL, P〈0.0001 vs DM）, glial activation, and active caspase-3 （P〈0.0001 vs CTL, P〈0.0001 vs DM） were blocked in diabetic retinas of AE extract-fed mice. Expression levels of protein O-GIcNAcylation and OGT were increased in diabetic retinas （P〈0.0001 vs CTL）, and the level of O-GIcNAcylation of the NF-KB p65 subunit was higher in diabetic retinas than in controls （P〈0.0001 vs CTL）. AE extract downregulated O-GIcNAcylation of NF-KB and prevented neurodegeneration induced by hyperglycemia （P〈0.0001 vs DM）. CONCLUSION： O-GIcNAcylation of NF-KB is concerned in neuronal degeneration and that AE prevents diabetes-in- duced RGC apoptosis via downregulation of NF-KB O-GI- cNAcylation. Hence, O-GIcNAcylation may be a new object for the treatment of DR, and AE may have therapeutic pos- sibility to prevent diabetes-induced neurodegeneration.展开更多
AIM:To investigate the role of autophagy inhibitor 3-methyladenine(3-MA)on a diabetic mice model(DM)and the potential mechanism.METHODS:Male C57BL/6J mice were randomly divided into a normal control group(NC group)and...AIM:To investigate the role of autophagy inhibitor 3-methyladenine(3-MA)on a diabetic mice model(DM)and the potential mechanism.METHODS:Male C57BL/6J mice were randomly divided into a normal control group(NC group)and an DM group.DM were induced by multiple low-dose intraperitoneal injection of streptozotocin(STZ)60 mg/kgd for 5 consecutive days.DM mice were randomly subdivided into untreated group(DM group),3-MA(10 mg/kgd by gavage)treated group(DM+3-MA group)and chloroquine(CQ;50 mg/kg by intraperitoneal injection)treated group(DM+CQ group).The fasting blood glucose(FBG)levels were recorded every week.At the end of experiment,retinal samples were collected.The expression levels of pro-apoptotic proteins cleaved caspase-3,cleaved poly ADP-ribose polymerase 1(PARP1)and Bax,anti-apoptotic protein Bcl-2,fibrosisassociated proteins Fibronectin and type 1 collagenα1 chain(COL1A1),vascular endothelial growth factor(VEGF),inflammatory factors interleukin(IL)-1βand tumor necrosis factor(TNF)-α,as well as autophagy related proteins LC3,Beclin-1 and P62 were determined by Western blotting.The oxidative stress indicators 8-hydroxydeoxyguanosine(8-OHdG)and malondialdehyde(MDA)were detected by commercial kits.RESULTS:Both 3-MA and CQ had shor t-term hypoglycemic effect on FBG and reduced the expression of VEGF and inflammatory factors IL-1βand TNF-αin DM mice.3-MA also significantly alleviated oxidative stress indicators 8-OHdG and MDA,decreased the expression of fibrosisrelated proteins Fibronectin and COL1A1,pro-apoptotic proteins cleaved caspase-3,cleaved PARP1,as well as the ratio of Bax/Bcl-2.CQ had no significant impact on the oxidative stress indicators,fibrosis,and apoptosis related proteins.The results of Western blotting for autophagy related proteins showed that the ratio of LC3 II/LC3 I and the expression of Beclin-1 in the retina of DM mice were decreased by 3-MA treatment,and the expression of P62 was further increased by CQ treatment.CONCLUSION:3-MA has anti-apoptotic and anti-fibrotic effects on the retina of DM mice,and can attenuate retinal oxidative stress,VEGF expression and the production of inflammatory factors in the retina of DM mice.The underlying mechanism of the above effects of 3-MA may be related to its inhibition of early autophagy and hypoglycemic effect.展开更多
Objective: To observe the effects of Bushen Huoxue Formula (Formula for reinforcing the kidney and activating blood circulation) on the learning and memory function and the cerebral neurotransmitters in diabetic mice....Objective: To observe the effects of Bushen Huoxue Formula (Formula for reinforcing the kidney and activating blood circulation) on the learning and memory function and the cerebral neurotransmitters in diabetic mice. Methods: Forty ICR mice were randomized into the normal control group, model group, Nimotop group and Chinese medicine group, 10 mice in each group. Tail intravenous injection of alloxan was applied to prepare diabetic model. Four weeks later, intragastric administration of Bushen Huoxue Formula for the Chinese medicine group, Nimotop for the Nimotop group, and isometric distilled water for the other two groups were respectively given for 8 weeks. The changes in the blood sugar level were observed; the learning and memory function was detected by Morris labyrinth test; and the contents of norepinephrine (NE), dopamine (DA), 5-hydroxyltryptamine (5-HT) and 5-hydroxyl indole acetic acid (5-HIAA) in cerebral cortex were determined in mice of all the groups. Results: The blood sugar levels in the diabetic model mice significantly increased as compared with those of the normal control group determined 72 h and 12 weeks later (P<0.05 or P<0.01). Latencies for Morris labyrinth test in the Nimotop group and the Chinese medicine group were significantly shortened as compared with that in the model group (P<0.01). The contents of cortical NE in the Chinese medicine group was significantly higher than that in the model group (P<0.01). Conclusion: Bushen Huoxue Formula can improve the learning and memory function in the diabetic mice, and the mechanism is possibly related with change of the cortical NE content.展开更多
Background: To study the antidiabetic effects and mechanisms of the fenugreek extracts in streptozotocin(STZ)-induced type 2 diabetic(T2 DM) mice fed a high-fat diet(HFD).Methods: We established C57 BL/6 J mice model ...Background: To study the antidiabetic effects and mechanisms of the fenugreek extracts in streptozotocin(STZ)-induced type 2 diabetic(T2 DM) mice fed a high-fat diet(HFD).Methods: We established C57 BL/6 J mice model of T2 DM using HFD-fed and STZinduced method. Then, the mice were administered with two types of fenugreek extracts(E1, flavonoid and E2, stilbene glycoside) for 4 weeks and the effects on fasting blood glucose(FBG), weight, superoxide dismutase(SOD), catalase(CAT),malondialdehyde(MDA), and pathological indexes were investigated.Results: Administration of fenugreek extracts decreased the FBG level compared with that of the model group. Comparatively, the high-dose E2 decreased the FBG more significantly than the other treatments did. Both extracts showed an obvious antioxidant effect by increasing serum SOD and CAT activities and decreasing the MDA content. Furthermore, the high-dose E1 showed a significant difference(P <.01) compared with the model group in the three investigated indexes.Conclusion: Our study demonstrated that both the flavonoid and stilbene glycoside extracts of fenugreek improved the hyperglycemia in the T2 DM mice model. Moreover, the antidiabetic effects of both extracts might be due to their antioxidant activity in vivo.展开更多
The peroxisome proliferator-activated receptor(PPARδ)agonists are reported to improve insulin sensitivity,reduce glucose levels,and alleviate dysfunctional lipid metabolism in animal models of type 2 diabetes mellitu...The peroxisome proliferator-activated receptor(PPARδ)agonists are reported to improve insulin sensitivity,reduce glucose levels,and alleviate dysfunctional lipid metabolism in animal models of type 2 diabetes mellitus.However,the underlying mechanisms remain incompletely understood.Metabolism plays an essential role in the biological system.Monitoring of metabolic changes in response to disease conditions or drug treatment is critical for better understanding of the pathophysiological mechanisms.In this study,metabolic profiling analysis by gas chromatography-mass spectrometry integrated with targeted analysis by liquid chro matography-mass spectrometry was carried out in plasma samples of db/db diabetic mice after six-week treatment of PPARδagonist GW501516.GW501516 treatment significantly altered levels of metabolites,such as branched-chain amino acids(BCAAs),BCAA metabolites(3-hydroxyisobutyric acid and 3-hydroxyisovaleric acid),long-chain fatty acids,uric acid and ketone bodies(3-hydroxybutyric acid and 2-hydroxybutyric acid)which are all associated with the impaired systemic insulin sensitivity.The pre sent results indicate the beneficial effect of PPARδagonist in alleviating insulin resistance of diabetic mice by favorably modulating metabolic profile,thus providing valuable information in understanding the therapeutic potential of PPARδagonists in correcting metabolic dysfunction in diabetes.展开更多
Diabetes mellitus affects an estimated 422 million people worldwide.Peripheral neuropathy is one of the most common and disabling complications of diabetes.There is currently no effective treatment for diabetic neurop...Diabetes mellitus affects an estimated 422 million people worldwide.Peripheral neuropathy is one of the most common and disabling complications of diabetes.There is currently no effective treatment for diabetic neuropathy,展开更多
The therapeutic effect of gamma-aminobutyric acid(GABA)on diabetes was spread as one of the alarming epidemics worldwide.The study aims to investigate the function of Lactobacillus brevis KLDS_(1.0727) and KLDS_(1.037...The therapeutic effect of gamma-aminobutyric acid(GABA)on diabetes was spread as one of the alarming epidemics worldwide.The study aims to investigate the function of Lactobacillus brevis KLDS_(1.0727) and KLDS_(1.0373) strains as glutamic acid decarboxylase 65(GAD65)carriers capable of generating GABA by comparing in vitro free and freeze-dried models and GABA intervention in vivo.PCR amplification of gad and in vitro i.e.,(growth rate,viability at different pH,bile tolerance,and survivability in simulated gastric juice)were performed.In vivo experiments were conducted in 7 groups of C57BL/6J mice.Each group was injected with streptozotocin(Cont_(STZ),INSSTZ,LAC1_(STZ),LAC_(1MFDSTZ),LAC_(2STZ),LAC_(2MFDSTZ))daily except for the control(Cont).One group was injected with insulin(INSSTZ).The body weight and hyperglycemia in the blood were assessed weekly,post-euthanasia blood plasma parameters,insulin,and histological examination were evaluated.Results indicated L.brevis strains demonstrated a great tolerance to bile and simulated gastric juice in vitro(P<0.05).Cont_(STZ) had the highest average glucose level(6.84±6.46)mmol/L while INS_(STZ) expressed dramatically decreed in glucose level and displayed a significant decline in the average of weekly blood glucose(−5.74±3.08)mmol/L.The lowest body weight(ContSTZ)was(19.30±0.25)g.Based on the blood plasma analysis,L.brevis strains improved good cholesterol properties,liver and kidney functions,where most of these parameters fall within the average the reference range and prevent the development of symptoms of type 1 diabetes in vivo.As recommended,L.brevis should be commonly distributed as a postbiotic GABA in pharmaceutical and nutritional applications.展开更多
AIM: To test whether oral L-81 treatment could im-prove the condition of mice with diabetes and to investigate how L-81 regulates microsomal triglyceride transfer protein (MTP) activity in the liver. METHODS: Genetica...AIM: To test whether oral L-81 treatment could im-prove the condition of mice with diabetes and to investigate how L-81 regulates microsomal triglyceride transfer protein (MTP) activity in the liver. METHODS: Genetically diabetic (db/db) mice were fed on chow supplemented with or without L-81 for 4 wk. The body weight, plasma glucose level, plasma lipid profile, and adipocyte volume of the db/db mice were assessed after treatment. Toxicity of L-81 was also evaluated. To understand the molecular mecha-nism, HepG2 cells were treated with L-81 and the effects on apolipoprotein B (apoB) secretion and mRNA level of the MTP gene were assessed.RESULTS: Treatment of db/db mice with L-81 sig-nificantly reduced and nearly normalized their body weight, hyperphagia and polydipsia. L-81 also markedly decreased the fasting plasma glucose level, improved glucose tolerance, and attenuated the elevated levels of plasma cholesterol and triglyceride. At the effective dosage, little toxicity was observed. Treatment of HepG2 cells with L-81 not only inhibited apoB secretion, but also signif icantly decreased the mRNA level of the MTP gene. Similar to the action of insulin, L-81 exerted its effect on the MTP promoter. CONCLUSION: L-81 represents a promising candidate in the development of a selective insulin-mimetic mol-ecule and an anti-diabetic agent.展开更多
BACKGROUND As one of the major microvascular complications of diabetes,diabetic retinopathy(DR)is the leading cause of blindness in the working age population.Because the extremely complex pathogenesis of DR has not b...BACKGROUND As one of the major microvascular complications of diabetes,diabetic retinopathy(DR)is the leading cause of blindness in the working age population.Because the extremely complex pathogenesis of DR has not been fully clarified,the occurrence and development of DR is closely related to tissue ischemia and hypoxia and neovascularization The formation of retinal neovascularization(RNV)has great harm to the visual acuity of patients.AIM To investigate the expression of P-element-induced wimpy testis-interacting RNA(piRNA)in proliferative DR mice and select piRNA related to RNV.METHODS One hundred healthy C57BL/6J mice were randomly divided into a normal group as control group(CG)and proliferative DR(PDR)group as experimental group(EG),with 50 mice in each group.Samples were collected from both groups at the same time,and the lesions of mice were evaluated by hematoxylin and eosin staining and retinal blood vessel staining.The retinal tissues were collected for second-generation high-throughput sequencing,and the differentially expressed piRNA between the CG and EG was detected,and polymerase chain reaction(PCR)was conducted for verification.The differentially obtained piRNA target genes and expression profiles were enrichment analysis based on gene annotation(Gene Ontology)and Kyoto Encyclopedia of Genes and Genomes.RESULTS In the CG there was no perfusion area,neovascularization and endothelial nucleus broke through the inner boundary membrane of retinap.In the EG,there were a lot of nonperfused areas,new blood vessels and endothelial nuclei breaking through the inner boundary membrane of the retina.There was a statistically significant difference in the number of vascular endothelial nuclei breaking through the inner retinal membrane between the two groups.High-throughput sequencing analysis showed that compared with the CG,a total of 79 piRNAs were differentially expressed in EG,among which 43 piRNAs were up-regulated and 36 piRNAs were down-regulated.Bioinformatics analysis showed that the differentially expressed piRNAs were mainly concentrated in the signaling pathways of angiogenesis and cell proliferation.Ten piRNAs were selected for PCR,and the results showed that the expression of piR-MMU-40373735,piRMMU-61121420,piR-MMU-55687822,piR-MMU-1373887 were high,and the expression of piR-MMU-7401535,piR-MMU-4773779,piR-MMU-1304999,and piR-MMU-5160126 were low,which were consistent with the sequencing results.CONCLUSION In the EG,the abnormal expression of piRNA is involved in the pathway of angiogenesis and cell proliferation,suggesting that piRNAs have some regulatory function in proliferative diabetic-retinopathy.展开更多
Streptozotocin (STZ)-induced diabetic mice increased levels of serum glucose, triglyceride and cholesterol, and decreased level of serum insulin. Effects of Bofutsushosan (BOF: Pulvis ledebouriellae compositae: 防風...Streptozotocin (STZ)-induced diabetic mice increased levels of serum glucose, triglyceride and cholesterol, and decreased level of serum insulin. Effects of Bofutsushosan (BOF: Pulvis ledebouriellae compositae: 防風通聖散) and its composed crude drug, gardeniae fructus (GF: 山梔子) were investigated on levels of these diabetic parameters (serum glucose, insulin, triglyceride and cholesterol) in STZ-diabetic mice. BOF and GF were extracted in 10 volumes of distilled water with an automatic extractor “Torobi”. STZ-induced diabetic mice with serum glucose level of over 600 mg/dl at 3 - 4 weeks after intravenous injection of 150 mg/kg STZ were used for experiments. BOF extract, GF extract, geniposide (a main constituent of GF), and glibenclamide were administered intraperitoneally into 3-hour-fasted STZ-diabetic mice. At 6 hours after administration, BOF extract (100 - 300 mg/kg) decreased high levels of serum glucose, triglyceride and cholesterol, and also increased low level of serum insulin in STZ-diabetic mice in a dose-dependent manner, respectively. Anti-diabetic drug glibenclamide (0.3 - 1 mg/kg) as positive control significantly decreased serum glucose and cholesterol levels, and increased serum insulin level in the diabetic mice. GF extract (30 - 300 mg/kg) decreased serum glucose, triglyceride and cholesterol levels but did not affect serum insulin level in the diabetic mice. Geniposide (10 - 100 mg/kg), decreased serum glucose level but did not affect serum insulin and triglyceride levels in the diabetic mice. These results demonstrated that intraperitoneally administrated BOF extract improved abnormal levels of serum glucose, insulin, triglyceride and cholesterol in the STZ-diabetic mice as being similar to glibenclamide. GF extract has an important role in a part of improving actions of BOF in the diabetic mice. The action of GF extract on serum glucose was parallel with the action of geniposide in the diabetic mice, supporting roles of geniposide in anti-hyperglycemic action of GF.展开更多
Objective To clarify the differences in cardiac structure,cardiac function,and myocardial metabolism in type 2 diabetes mellitus mice with obesity or non-obesity and to elucidate the key molecular mechanisms leading t...Objective To clarify the differences in cardiac structure,cardiac function,and myocardial metabolism in type 2 diabetes mellitus mice with obesity or non-obesity and to elucidate the key molecular mechanisms leading to this difference.Methods Db/db mice and low-dose STZ injection combined with HFD-induced diabetes mellitus mice were used in this study as the model of type 2 diabetes mellitus with obesity or non-obesity.展开更多
Objective:To investigate the effect of administration of Passiflora glandulosa(P.glandulosa) fruit rinds flour on streptozotocin(STZ)-induced diabetic mice.Methods:The preliminary phytochemical screening and parameter...Objective:To investigate the effect of administration of Passiflora glandulosa(P.glandulosa) fruit rinds flour on streptozotocin(STZ)-induced diabetic mice.Methods:The preliminary phytochemical screening and parameters such as centesimal composition and brine shrimp toxicity were evaluated.For in vivo study Swiss female mice were divided into four groups:NC-normal control;DC-diabetic control animals receiving saline;MET-diabetic animals receiving metformin(200 mg/kg);PFRF-diabetic animals receiving P.glandulosa fruit rinds flour(200 mg/kg).All of them were treated for 28 d.STZ was used in a single dose of 120 mg/kg to establish diabetic models.Body weight,water and food intake,fasting blood glucose were measured.Histopathological analysis of pancreas and liver were performed to evaluate STZ-induced tissue injuries.Results:Phytochemical screening showed the presence of flavanones and triterpenoids.The P.glandulosa fruit rinds flour was non-toxic by the brine shrimp test.The fruit rinds flour also reduced the loss of body weight and significantly decreased food intake in the diabetic mice.Additionally,a significant reduction in blood glucose was observed for 15 d and this was maintained on 21 d and 28 d when compared with diabetic mice.Furthermore,the P.glandulosa fruit rinds flour has a favourable effect on the histopathological changes of the pancreas in STZ induced diabetes.Conclusions:It is concluded that P.glandulosa fruit rinds flour is a natural product that contains potent antioxidant compounds and presents good prospects for the improvement of diabetic mellitus by reducing serum glucose levels.展开更多
The aim of this study was to evaluate the effect of chronic treatment with diets rich in carbohydrates on the IgM and IgG antibody production and the seric glucose concentration in diabetes. Nonobese diabetic (NOD) mi...The aim of this study was to evaluate the effect of chronic treatment with diets rich in carbohydrates on the IgM and IgG antibody production and the seric glucose concentration in diabetes. Nonobese diabetic (NOD) mice received, ad libitum, by oral route, the diet consisting of an aqueous extract (20 mg/mL) of the following flours: babassu mesocarp, manioc, corn or rice, during 120 days. The diet intake was monitored throughout this period. At the end, the weight variation, blood glucose, serum IgG and IgM antibody and IgM anti-insulin titers, were determined. The babassu and manioc flour extracts altered Purina chow intake and these animals also presented a significant increase in body weight. In contrast, treatment with rice flour resulted in a significant weight loss. Moderate to severe hyperglycemia was observed in the groups receiving rice and manioc, whereas treatment with babassu mesocarp flour and cornmeal resulted in hypoglycemia. The extracts did not alter the IgG concentration. On the other hand, the cornmeal extract caused a marked reduction in both total IgM and anti-insulin IgM antibody production. Although babassu mesocarp flour, cornmeal and manioc flour caused important variations in the parameters studied, only treatment with the rice flour extract anticipated the onset of diabetes in male mice genetically predisposed to the disease.展开更多
文摘Type 1 diabetes mellitus results from the autoimmune and inflammatory destruction of insulin-producing islet β cells, rendering individuals devoid of insulin production. Recent studies suggest that combination therapies consisting of anti-inflammatory agents and islet growth-promoting factors have the potential to cause sustained recovery of β cell mass, leading to amelioration or reversal of type 1 diabetes in mouse models. In this study, we hypothesized that the combination of the anti-inflammatory agent lisofylline (LSF) with an active peptide fragment of islet neogenesis associated protein (INGAP peptide) would lead to remission of type 1 diabetes in the non-obese diabetic (NOD) mouse. We treated groups of spontaneously diabetic NOD mice with combinations of LSF, INGAP peptide, or control saline parenterally for up to 6 weeks. Our results demonstrate that the mice receiving combined treatment with LSF and INGAP peptide exhibited partial remission of diabetes with increased plasma insulin levels. Histologic assessment of pancreata in mice receiving combined therapy revealed the presence of islet insulin staining, increased β cell replication, and evidence of Pdx1-positivity in ductal cells. By contrast, diabetic animals showed severe insulitis with no detectible insulin or Pdx1 staining. We conclude that the novel combination treatment with LSF and INGAP peptide has the potential to ameliorate hyperglycemia in the setting of established type 1 diabetes via the recovery of endogenous β cells and warrant further studies.
文摘The relationships between five classes of Japanese people （i.e., 96 centenarians, 96 Alzheimer＇s disease （AD） patients, 96 Parkinson＇s disease （PD） patients, 96 type 2 diabetic （T2D） patients, and 96 healthy non-obese young males） and their mitochondrial single nucleotide polymorphism （mtSNP） frequencies at individual mtDNA positions of the entire mitochondrial genome were examined using the radial basis function （RBF） network and the modified method. New findings of mitochondrial haplogroups were obtained for individual classes. The five classes of people were associated with the following haplogroups： Japanese centenarians-M7b2, D4b2a, and B5b; Japanese AD patients-G2a, B4cl, and N9b1; Japanese PD patients-M7b2, B4e, and B5b; Japanese T2D patients-B5b, M8al, G, D4, and F1; and Japanese healthy non-obese young males-D4g and D4b1b. From the points of common haplogroups among the five classes, the cente- narians have the common haplogroups M7b2 and B5b with the PD patients and common haplogroup B5b with the T2D patients. In addition, the 112 Japanese semi-supercentenarians （over 105 years old） recently reported were also examined by the method proposed. The results obtained were the haplogroups D4a, B4c1a, M7b2, F1, M1, and B5b. These results are different from the previously reported haplogroup classifications. As the proposed analysis method can predict a person＇s mtSNP constitution and the probabilities of becoming a centenarian, AD patient, PD patient, or T2D patient, it may be useful in initial diagnosis of various diseases.
文摘BACKGROUND: Triptolide (TPT) is a diterpenoid triepoxide extracted from the Chinese herb Tripterygium wilfordii Hook. F. It exhibits potent immunosuppressive and anti-inflammatory properties. This study was undertaken to investigate its effects on prolongation of islet allograft survival in rodents. Additionally, we investigated whether TPT would be toxic to islet function in vivo. METHODS: We transplanted BALB/c islets to either chemically induced diabetic C57BL/6 mice or spontaneously diabetic non-obese diabetic (NOD) mice. TPT was injected within 2 weeks or continuously, until rejection, in the two combinations. Then, we evaluated the toxicity of TPT on islet function by daily injection to naive BALB/c or diabetic BALB/c that was cured by syngeneic islet transplantation under the kidney capsule. Mice injected with cyclosporine A (CsA) or vehicle served as controls. Intraperitoneal glucose tolerance tests (IPGTTs) performed at 4 and 8 weeks in the naive BALB/c group, and at 2, 4, 6, and 8 weeks in the syngeneic transplanted group. RESULTS: The medium survival time of islets allograft from TPT treated C57BL/6 and NOD recipients were 28.5 days (range 24-30 days, n=10) and 33.0 days (range 15-47 days, n=6), respectively, and they were significantly different from those of the vehicle treated controls, which were 14.0 days (range 13-16 days, n=6) and 5.0 days (range 4-10 days, n=6), respectively (all P<0.0001). The IPGTT demonstrated that there was no difference between the TPT treated and vehicle treated groups, either in the normal or syngeneic transplanted islet BALB/c mice. However, CsA injection impaired islet function in both normal and syngeneic transplanted mice as early as 4 weeks. CONCLUSION: TPT prolonged islets allograft survival in a chemically induced diabetic or an autoimmune diabetic murine model without impairment of islet function. (Hepatobiliary Pancreat Dis Int 2010; 9: 312-318)
文摘Aim To study the effects of binuclear copper （Ⅱ） threonine complex （Cu2 （Thr）4） as analogue of superoxide dismutase （SOD） on blood glucose, blood lipids and vessels of hearts and kidneys in diabetic mice. Methods Diabetic mouse model was established by intraperitioneal injection of alloxan. Low, middle, and high doses of Cu2（Thr）4 at 0.002%, 0.02% and 0.1% were given respectively to diabetic mice following lavage. The fasting blood glucose was determined after the diabetic mice were given Cu2 （Thr）4 for 0, 30, and 45 d. The diabetic mice were killed on the 45th day. Then glycosylated hemoglobin （HbAlc） and blood lipids were assayed, and pathologic changes in hearts and kidneys stained with HE were observed. Results Compared with the control group in which the diabetic mice were given distilled water, the value of blood glucose reduced significantly in middle dose group （P 〈 0.01 ）, followed by that in low dose group （P 〈 0.05）. TC level reduced markedly and HDL level increased significantly in all three treatment groups （P 〈 0.05）. Especially in middle dose group, cardiac muscle fibers were neatly arranged, nucleus and cytoplasm well distributed, glomeruli showing normal structure, cells well distributed and staining being normal. Conclusion Cu2 （Thr）4 reduces blood glucose, regulates blood lipids, and play protective action on the vessels of hearts and kidneys in diabetic mice. The effects of it in middle dose were better than those of other doses.
基金New-Century Talent Program,Ministry of Educating of China(Grant No.985-2-102-113)National Key Technology R&D Program"New Drug Innovation"of China(Grant No.2009ZX09311-004,2012ZX09301-002-002-002)
文摘The leaves of Aquilaria sinensis（Lour.） Gilg have been used in folk medicine for the treatment of diabetes in Guangdong Province,China.In this study,effects of ethanol extract of Aquilaria sinensis leaves on hyperglycemia were investigated in diabetic db/db mice.After 4 weeks of administration,the 95%ethanol（EtOH） extract of Aquilaria sinensis leaves （AE）,especially at high dose level（600 mg/kg）,activated AMP-activated protein kinase（AMPK）,resulting in reduced fasting blood glucose and glycosylated hemoglobin levels in db/db mice.In addition,the oral glucose tolerance test（OGTT test） showed that AE could remarkably improve insulin resistance.Compared to Thiazolinediones（TZDs）,no weight gain was observed after AE administration,which is a severe side effect of TZDs.The data suggested that AE could act as an activator of AMPK,and might be used as an alternative to TZDs in the management of obesity-related diabetes.
基金the Ministry of Higher Education Malaysia(grant FRGS 5/3[273/2019])the Universiti Teknologi MARA(grant MYRA 5/3/MITRA[008/2017]-2).
文摘Diabetes mellitus(DM)is known to cause reproductive impairment.In men,it has been linked to altered sperm quality and testicular damage.Oxidative stress(OS)plays a pivotal role in the development of DM complications.Glutathione(GSH)is a part of a nonenzymatic antioxidant defense system that protects lipid,protein,and nucleic acids from oxidative damage.However,the protective effects of exogenous GSH on the male reproductive system have not been comprehensively examined.This study determined the impact of GSH supplementation in ameliorating the adverse effect of type 1 DM on sperm quality and the seminiferous tubules of diabetic C57BL/6NTac mice.GSH at the doses of 15 mg kg^(-1)and 30 mg kg^(-1)was given intraperitoneally to mice weekly for 6 consecutive weeks.The mice were then weighed,euthanized,and had their reproductive organs excised.The diabetic(D Group)showed significant impairment of sperm quality and testicular histology compared with the nondiabetic(ND Group).Diameters of the seminiferous lumen in diabetic mice treated with 15 mg kg^(-1) GSH(DGSH15)were decreased compared with the D Group.Sperm motility was also significantly increased in the DGSH15 Group.Improvement in testicular morphology might be an early indication of the protective roles played by the exogenous GSH in protecting sperm quality from effects of untreated type 1 DM or diabetic complications.Further investigation using different doses and different routes of GSH is necessary to confirm this suggestion.
基金National Nature Science Foundation of China, No. 30400429
文摘AIM:To investigate the potential therapeutic significance of ghrelin and growth hormone releasing peptide 6 (GHRP-6) in diabetic mice with gastric motility disorders. METHODS: A diabetic mouse model was established by intraperitoneal (ip) injection of alloxan. Diabetic mice were injected ip with ghrelin or GHRP-6 (20-200 μg/kg), and the effects on gastric emptying were measured after intragastric application of phenol red. The effect of atropine, NG-nitro-L-arginine methyl ester hydrochloride (L-NAME) or D-Lys3-GHRP-6 (a growth hormone secretagogue receptor (GHS-R) antagonist) on the gastroprokinetic effect of ghrelin or GHRP-6 (100 μg/kg) was also investigated. The effects of ghrelin or GHRP-6 (0.01-10 μmol/L) on spontaneous or carbachol-induced contractile amplitude were also investigated in vitro, in gastric fundic circular strips taken from diabetic mice. The presence of growth hormone secretagogue receptor 1a transcripts in the fundic strips of diabetic mice was detected by reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: We established a diabetic mouse model with delayed gastric emptying. Ghrelin and GHRP-6 accelerated gastric emptying in diabetic mice with gastroparesis. In the presence of atropine or L-NAME, which delayed gastric emptying, ghrelin and GHRP-6 (100 μg/kg) failed to accelerate gastric emptying. D-Lys3-GHRP-6 also delayed gastric emptying induced by the GHS-R agonist. Ghrelin and GHRP-6 increased the carbachol-induced contractile amplitude in gastric fundicstrips taken from diabetic mice. RT-PCR confirmed the presence of GHS-R mRNA in the strip preparations. CONCLUSION: Ghrelin and GHRP-6 increase gastric emptying in diabetic mice with gastroparesis, perhaps by activating peripheral cholinergic pathways in the enteric nervous system.
基金Supported by the Basic Science Research Program Through the National Research Foundation(NRF)of Korea Funded by the Ministry of Science,ICT,and Future Planning 2014049413,NRF-2015R1A5A2008833 and NRF-2015R1C1A1A02037702
文摘AIM： To investigate the role of O-GIcNAcylation of nuclear factor-kappa B （NF-KB） in retinal ganglion cell （RGC） death and analysedthe effect of Aralia elata （AE） on neurodegen- eration in diabetic mice. METHODS： C57BL/6mice with streptozotocin-induced diabetes were fed daily with AE extract or control （CTL） diet at the onset of diabetes mellitus （DM）. Two months af- tar injection of streptozotocin or saline, the degree of cell death and the expression of O-GIcNAc transferase （OGT）, N-acetyl-b-D-glucosaminidase （OGA）, O-GIcNAcylated pro- teins, and O-GIcNAcylation of NF-KB were examined. RESULTS： AE did not affect the metabolic status of diabetic mice. The decrease in the inner retinal thickness （P〈0.001 vs CTL, P〈0.01 vs DM） and increases in RGCs with terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling （P〈0.001 vs CTL, P〈0.0001 vs DM）, glial activation, and active caspase-3 （P〈0.0001 vs CTL, P〈0.0001 vs DM） were blocked in diabetic retinas of AE extract-fed mice. Expression levels of protein O-GIcNAcylation and OGT were increased in diabetic retinas （P〈0.0001 vs CTL）, and the level of O-GIcNAcylation of the NF-KB p65 subunit was higher in diabetic retinas than in controls （P〈0.0001 vs CTL）. AE extract downregulated O-GIcNAcylation of NF-KB and prevented neurodegeneration induced by hyperglycemia （P〈0.0001 vs DM）. CONCLUSION： O-GIcNAcylation of NF-KB is concerned in neuronal degeneration and that AE prevents diabetes-in- duced RGC apoptosis via downregulation of NF-KB O-GI- cNAcylation. Hence, O-GIcNAcylation may be a new object for the treatment of DR, and AE may have therapeutic pos- sibility to prevent diabetes-induced neurodegeneration.
基金Supported by the National Natural Science Foundation of China(No.82270893)Joint Fund of Health Committee of Hubei Province(No.WJ2019-16).
文摘AIM:To investigate the role of autophagy inhibitor 3-methyladenine(3-MA)on a diabetic mice model(DM)and the potential mechanism.METHODS:Male C57BL/6J mice were randomly divided into a normal control group(NC group)and an DM group.DM were induced by multiple low-dose intraperitoneal injection of streptozotocin(STZ)60 mg/kgd for 5 consecutive days.DM mice were randomly subdivided into untreated group(DM group),3-MA(10 mg/kgd by gavage)treated group(DM+3-MA group)and chloroquine(CQ;50 mg/kg by intraperitoneal injection)treated group(DM+CQ group).The fasting blood glucose(FBG)levels were recorded every week.At the end of experiment,retinal samples were collected.The expression levels of pro-apoptotic proteins cleaved caspase-3,cleaved poly ADP-ribose polymerase 1(PARP1)and Bax,anti-apoptotic protein Bcl-2,fibrosisassociated proteins Fibronectin and type 1 collagenα1 chain(COL1A1),vascular endothelial growth factor(VEGF),inflammatory factors interleukin(IL)-1βand tumor necrosis factor(TNF)-α,as well as autophagy related proteins LC3,Beclin-1 and P62 were determined by Western blotting.The oxidative stress indicators 8-hydroxydeoxyguanosine(8-OHdG)and malondialdehyde(MDA)were detected by commercial kits.RESULTS:Both 3-MA and CQ had shor t-term hypoglycemic effect on FBG and reduced the expression of VEGF and inflammatory factors IL-1βand TNF-αin DM mice.3-MA also significantly alleviated oxidative stress indicators 8-OHdG and MDA,decreased the expression of fibrosisrelated proteins Fibronectin and COL1A1,pro-apoptotic proteins cleaved caspase-3,cleaved PARP1,as well as the ratio of Bax/Bcl-2.CQ had no significant impact on the oxidative stress indicators,fibrosis,and apoptosis related proteins.The results of Western blotting for autophagy related proteins showed that the ratio of LC3 II/LC3 I and the expression of Beclin-1 in the retina of DM mice were decreased by 3-MA treatment,and the expression of P62 was further increased by CQ treatment.CONCLUSION:3-MA has anti-apoptotic and anti-fibrotic effects on the retina of DM mice,and can attenuate retinal oxidative stress,VEGF expression and the production of inflammatory factors in the retina of DM mice.The underlying mechanism of the above effects of 3-MA may be related to its inhibition of early autophagy and hypoglycemic effect.
基金supported by the Foundation of Peking Union Medical College Hospital, China (XH-020042)
文摘Objective: To observe the effects of Bushen Huoxue Formula (Formula for reinforcing the kidney and activating blood circulation) on the learning and memory function and the cerebral neurotransmitters in diabetic mice. Methods: Forty ICR mice were randomized into the normal control group, model group, Nimotop group and Chinese medicine group, 10 mice in each group. Tail intravenous injection of alloxan was applied to prepare diabetic model. Four weeks later, intragastric administration of Bushen Huoxue Formula for the Chinese medicine group, Nimotop for the Nimotop group, and isometric distilled water for the other two groups were respectively given for 8 weeks. The changes in the blood sugar level were observed; the learning and memory function was detected by Morris labyrinth test; and the contents of norepinephrine (NE), dopamine (DA), 5-hydroxyltryptamine (5-HT) and 5-hydroxyl indole acetic acid (5-HIAA) in cerebral cortex were determined in mice of all the groups. Results: The blood sugar levels in the diabetic model mice significantly increased as compared with those of the normal control group determined 72 h and 12 weeks later (P<0.05 or P<0.01). Latencies for Morris labyrinth test in the Nimotop group and the Chinese medicine group were significantly shortened as compared with that in the model group (P<0.01). The contents of cortical NE in the Chinese medicine group was significantly higher than that in the model group (P<0.01). Conclusion: Bushen Huoxue Formula can improve the learning and memory function in the diabetic mice, and the mechanism is possibly related with change of the cortical NE content.
基金National Natural Science Foundation of China,Grant/Award Number:31470426Open Project of State Key Laboratory of Plateau Ecology and Agriculture,Grant/Award Number:2016-KF-05+2 种基金Qinghai Provincial Science Foundation,Grant/Award Number:2016-ZJ-01,2016-ZJ-929QTaishan Scholar Program of Shandong Province,Grant/Award Number:tshw201502046Shandong Provincial Science Foundation,Grant/Award Number:ZR2017MH024
文摘Background: To study the antidiabetic effects and mechanisms of the fenugreek extracts in streptozotocin(STZ)-induced type 2 diabetic(T2 DM) mice fed a high-fat diet(HFD).Methods: We established C57 BL/6 J mice model of T2 DM using HFD-fed and STZinduced method. Then, the mice were administered with two types of fenugreek extracts(E1, flavonoid and E2, stilbene glycoside) for 4 weeks and the effects on fasting blood glucose(FBG), weight, superoxide dismutase(SOD), catalase(CAT),malondialdehyde(MDA), and pathological indexes were investigated.Results: Administration of fenugreek extracts decreased the FBG level compared with that of the model group. Comparatively, the high-dose E2 decreased the FBG more significantly than the other treatments did. Both extracts showed an obvious antioxidant effect by increasing serum SOD and CAT activities and decreasing the MDA content. Furthermore, the high-dose E1 showed a significant difference(P <.01) compared with the model group in the three investigated indexes.Conclusion: Our study demonstrated that both the flavonoid and stilbene glycoside extracts of fenugreek improved the hyperglycemia in the T2 DM mice model. Moreover, the antidiabetic effects of both extracts might be due to their antioxidant activity in vivo.
基金supported by Hong Kong Research Grants Council(No.C4024-16W)National Natural Science Foundation of China(No.91939302)Health and Medical Research Fund,Hong Kong Government(No.05161746)。
文摘The peroxisome proliferator-activated receptor(PPARδ)agonists are reported to improve insulin sensitivity,reduce glucose levels,and alleviate dysfunctional lipid metabolism in animal models of type 2 diabetes mellitus.However,the underlying mechanisms remain incompletely understood.Metabolism plays an essential role in the biological system.Monitoring of metabolic changes in response to disease conditions or drug treatment is critical for better understanding of the pathophysiological mechanisms.In this study,metabolic profiling analysis by gas chromatography-mass spectrometry integrated with targeted analysis by liquid chro matography-mass spectrometry was carried out in plasma samples of db/db diabetic mice after six-week treatment of PPARδagonist GW501516.GW501516 treatment significantly altered levels of metabolites,such as branched-chain amino acids(BCAAs),BCAA metabolites(3-hydroxyisobutyric acid and 3-hydroxyisovaleric acid),long-chain fatty acids,uric acid and ketone bodies(3-hydroxybutyric acid and 2-hydroxybutyric acid)which are all associated with the impaired systemic insulin sensitivity.The pre sent results indicate the beneficial effect of PPARδagonist in alleviating insulin resistance of diabetic mice by favorably modulating metabolic profile,thus providing valuable information in understanding the therapeutic potential of PPARδagonists in correcting metabolic dysfunction in diabetes.
基金supported by NINDS grants RO1 NS075084(LW)NIDDK RO1 DK097519(LW)
文摘Diabetes mellitus affects an estimated 422 million people worldwide.Peripheral neuropathy is one of the most common and disabling complications of diabetes.There is currently no effective treatment for diabetic neuropathy,
基金supported by grant from the National Key Research and Development Program of China(2018YFE0120500).
文摘The therapeutic effect of gamma-aminobutyric acid(GABA)on diabetes was spread as one of the alarming epidemics worldwide.The study aims to investigate the function of Lactobacillus brevis KLDS_(1.0727) and KLDS_(1.0373) strains as glutamic acid decarboxylase 65(GAD65)carriers capable of generating GABA by comparing in vitro free and freeze-dried models and GABA intervention in vivo.PCR amplification of gad and in vitro i.e.,(growth rate,viability at different pH,bile tolerance,and survivability in simulated gastric juice)were performed.In vivo experiments were conducted in 7 groups of C57BL/6J mice.Each group was injected with streptozotocin(Cont_(STZ),INSSTZ,LAC1_(STZ),LAC_(1MFDSTZ),LAC_(2STZ),LAC_(2MFDSTZ))daily except for the control(Cont).One group was injected with insulin(INSSTZ).The body weight and hyperglycemia in the blood were assessed weekly,post-euthanasia blood plasma parameters,insulin,and histological examination were evaluated.Results indicated L.brevis strains demonstrated a great tolerance to bile and simulated gastric juice in vitro(P<0.05).Cont_(STZ) had the highest average glucose level(6.84±6.46)mmol/L while INS_(STZ) expressed dramatically decreed in glucose level and displayed a significant decline in the average of weekly blood glucose(−5.74±3.08)mmol/L.The lowest body weight(ContSTZ)was(19.30±0.25)g.Based on the blood plasma analysis,L.brevis strains improved good cholesterol properties,liver and kidney functions,where most of these parameters fall within the average the reference range and prevent the development of symptoms of type 1 diabetes in vivo.As recommended,L.brevis should be commonly distributed as a postbiotic GABA in pharmaceutical and nutritional applications.
基金Supported by The Area of Excellence scheme of University Grants Committeethe Research Grant Council Grant, HKU 7642/05M to MCL, from Hong Kong
文摘AIM: To test whether oral L-81 treatment could im-prove the condition of mice with diabetes and to investigate how L-81 regulates microsomal triglyceride transfer protein (MTP) activity in the liver. METHODS: Genetically diabetic (db/db) mice were fed on chow supplemented with or without L-81 for 4 wk. The body weight, plasma glucose level, plasma lipid profile, and adipocyte volume of the db/db mice were assessed after treatment. Toxicity of L-81 was also evaluated. To understand the molecular mecha-nism, HepG2 cells were treated with L-81 and the effects on apolipoprotein B (apoB) secretion and mRNA level of the MTP gene were assessed.RESULTS: Treatment of db/db mice with L-81 sig-nificantly reduced and nearly normalized their body weight, hyperphagia and polydipsia. L-81 also markedly decreased the fasting plasma glucose level, improved glucose tolerance, and attenuated the elevated levels of plasma cholesterol and triglyceride. At the effective dosage, little toxicity was observed. Treatment of HepG2 cells with L-81 not only inhibited apoB secretion, but also signif icantly decreased the mRNA level of the MTP gene. Similar to the action of insulin, L-81 exerted its effect on the MTP promoter. CONCLUSION: L-81 represents a promising candidate in the development of a selective insulin-mimetic mol-ecule and an anti-diabetic agent.
基金Supported by National Natural Science Foundation of China,No.81570866.
文摘BACKGROUND As one of the major microvascular complications of diabetes,diabetic retinopathy(DR)is the leading cause of blindness in the working age population.Because the extremely complex pathogenesis of DR has not been fully clarified,the occurrence and development of DR is closely related to tissue ischemia and hypoxia and neovascularization The formation of retinal neovascularization(RNV)has great harm to the visual acuity of patients.AIM To investigate the expression of P-element-induced wimpy testis-interacting RNA(piRNA)in proliferative DR mice and select piRNA related to RNV.METHODS One hundred healthy C57BL/6J mice were randomly divided into a normal group as control group(CG)and proliferative DR(PDR)group as experimental group(EG),with 50 mice in each group.Samples were collected from both groups at the same time,and the lesions of mice were evaluated by hematoxylin and eosin staining and retinal blood vessel staining.The retinal tissues were collected for second-generation high-throughput sequencing,and the differentially expressed piRNA between the CG and EG was detected,and polymerase chain reaction(PCR)was conducted for verification.The differentially obtained piRNA target genes and expression profiles were enrichment analysis based on gene annotation(Gene Ontology)and Kyoto Encyclopedia of Genes and Genomes.RESULTS In the CG there was no perfusion area,neovascularization and endothelial nucleus broke through the inner boundary membrane of retinap.In the EG,there were a lot of nonperfused areas,new blood vessels and endothelial nuclei breaking through the inner boundary membrane of the retina.There was a statistically significant difference in the number of vascular endothelial nuclei breaking through the inner retinal membrane between the two groups.High-throughput sequencing analysis showed that compared with the CG,a total of 79 piRNAs were differentially expressed in EG,among which 43 piRNAs were up-regulated and 36 piRNAs were down-regulated.Bioinformatics analysis showed that the differentially expressed piRNAs were mainly concentrated in the signaling pathways of angiogenesis and cell proliferation.Ten piRNAs were selected for PCR,and the results showed that the expression of piR-MMU-40373735,piRMMU-61121420,piR-MMU-55687822,piR-MMU-1373887 were high,and the expression of piR-MMU-7401535,piR-MMU-4773779,piR-MMU-1304999,and piR-MMU-5160126 were low,which were consistent with the sequencing results.CONCLUSION In the EG,the abnormal expression of piRNA is involved in the pathway of angiogenesis and cell proliferation,suggesting that piRNAs have some regulatory function in proliferative diabetic-retinopathy.
文摘Streptozotocin (STZ)-induced diabetic mice increased levels of serum glucose, triglyceride and cholesterol, and decreased level of serum insulin. Effects of Bofutsushosan (BOF: Pulvis ledebouriellae compositae: 防風通聖散) and its composed crude drug, gardeniae fructus (GF: 山梔子) were investigated on levels of these diabetic parameters (serum glucose, insulin, triglyceride and cholesterol) in STZ-diabetic mice. BOF and GF were extracted in 10 volumes of distilled water with an automatic extractor “Torobi”. STZ-induced diabetic mice with serum glucose level of over 600 mg/dl at 3 - 4 weeks after intravenous injection of 150 mg/kg STZ were used for experiments. BOF extract, GF extract, geniposide (a main constituent of GF), and glibenclamide were administered intraperitoneally into 3-hour-fasted STZ-diabetic mice. At 6 hours after administration, BOF extract (100 - 300 mg/kg) decreased high levels of serum glucose, triglyceride and cholesterol, and also increased low level of serum insulin in STZ-diabetic mice in a dose-dependent manner, respectively. Anti-diabetic drug glibenclamide (0.3 - 1 mg/kg) as positive control significantly decreased serum glucose and cholesterol levels, and increased serum insulin level in the diabetic mice. GF extract (30 - 300 mg/kg) decreased serum glucose, triglyceride and cholesterol levels but did not affect serum insulin level in the diabetic mice. Geniposide (10 - 100 mg/kg), decreased serum glucose level but did not affect serum insulin and triglyceride levels in the diabetic mice. These results demonstrated that intraperitoneally administrated BOF extract improved abnormal levels of serum glucose, insulin, triglyceride and cholesterol in the STZ-diabetic mice as being similar to glibenclamide. GF extract has an important role in a part of improving actions of BOF in the diabetic mice. The action of GF extract on serum glucose was parallel with the action of geniposide in the diabetic mice, supporting roles of geniposide in anti-hyperglycemic action of GF.
文摘Objective To clarify the differences in cardiac structure,cardiac function,and myocardial metabolism in type 2 diabetes mellitus mice with obesity or non-obesity and to elucidate the key molecular mechanisms leading to this difference.Methods Db/db mice and low-dose STZ injection combined with HFD-induced diabetes mellitus mice were used in this study as the model of type 2 diabetes mellitus with obesity or non-obesity.
基金finacially supported by GBtech(GreenBean Biotecnologia)
文摘Objective:To investigate the effect of administration of Passiflora glandulosa(P.glandulosa) fruit rinds flour on streptozotocin(STZ)-induced diabetic mice.Methods:The preliminary phytochemical screening and parameters such as centesimal composition and brine shrimp toxicity were evaluated.For in vivo study Swiss female mice were divided into four groups:NC-normal control;DC-diabetic control animals receiving saline;MET-diabetic animals receiving metformin(200 mg/kg);PFRF-diabetic animals receiving P.glandulosa fruit rinds flour(200 mg/kg).All of them were treated for 28 d.STZ was used in a single dose of 120 mg/kg to establish diabetic models.Body weight,water and food intake,fasting blood glucose were measured.Histopathological analysis of pancreas and liver were performed to evaluate STZ-induced tissue injuries.Results:Phytochemical screening showed the presence of flavanones and triterpenoids.The P.glandulosa fruit rinds flour was non-toxic by the brine shrimp test.The fruit rinds flour also reduced the loss of body weight and significantly decreased food intake in the diabetic mice.Additionally,a significant reduction in blood glucose was observed for 15 d and this was maintained on 21 d and 28 d when compared with diabetic mice.Furthermore,the P.glandulosa fruit rinds flour has a favourable effect on the histopathological changes of the pancreas in STZ induced diabetes.Conclusions:It is concluded that P.glandulosa fruit rinds flour is a natural product that contains potent antioxidant compounds and presents good prospects for the improvement of diabetic mellitus by reducing serum glucose levels.
文摘The aim of this study was to evaluate the effect of chronic treatment with diets rich in carbohydrates on the IgM and IgG antibody production and the seric glucose concentration in diabetes. Nonobese diabetic (NOD) mice received, ad libitum, by oral route, the diet consisting of an aqueous extract (20 mg/mL) of the following flours: babassu mesocarp, manioc, corn or rice, during 120 days. The diet intake was monitored throughout this period. At the end, the weight variation, blood glucose, serum IgG and IgM antibody and IgM anti-insulin titers, were determined. The babassu and manioc flour extracts altered Purina chow intake and these animals also presented a significant increase in body weight. In contrast, treatment with rice flour resulted in a significant weight loss. Moderate to severe hyperglycemia was observed in the groups receiving rice and manioc, whereas treatment with babassu mesocarp flour and cornmeal resulted in hypoglycemia. The extracts did not alter the IgG concentration. On the other hand, the cornmeal extract caused a marked reduction in both total IgM and anti-insulin IgM antibody production. Although babassu mesocarp flour, cornmeal and manioc flour caused important variations in the parameters studied, only treatment with the rice flour extract anticipated the onset of diabetes in male mice genetically predisposed to the disease.
