Medicinal plants have a long history of use in China to treat diabetic symptoms.Ancient Chinese medical manuscripts and ethnobotanical surveys document plant remedies that continue to be actively used in China for the...Medicinal plants have a long history of use in China to treat diabetic symptoms.Ancient Chinese medical manuscripts and ethnobotanical surveys document plant remedies that continue to be actively used in China for the treatment of diabetic symptoms.Based on a systematic ancient Chinese medical manuscripts review in combination with ethnobotanical survey,16 medicinal plants for the traditional treatment of diabetic symptoms were identified for the evaluation of anti-insulin resistance bioactivity.The biological activity of 16 medicinal plants was tested on dexamethasone(DXMS)-induced insulin resistant HepG2 cells.The result shows that 11 of the 16 medicinal plants enhanced glucose uptake of DXMS-induced insulin resistant HepG2 cells,thereby demonstrating their ability to increase insulin sensitivity,other five medicinal plants including Astragalus membranaceus were found ineffective.The study shows that ancient Chinese medical manuscripts and ethnobotanical surveys on plants for the prevention and treatment of diabetic symptoms provide a promising knowledge base for drug discovery to mitigate the global diabetes epidemic.展开更多
Insulin resistance is an essential characteristic of type 2 diabetes mellitus(T2DM),which can be induced by glucotoxicity and adipose chronic inflammation.Mesenchymal stem cells(MSCs)and their exosomes were reported t...Insulin resistance is an essential characteristic of type 2 diabetes mellitus(T2DM),which can be induced by glucotoxicity and adipose chronic inflammation.Mesenchymal stem cells(MSCs)and their exosomes were reported to ameliorate T2DM and its complications by their immunoregulatory and healing abilities.Exosomes derived from MSCs contain abundant molecules to mediate crosstalk between cells and mimic biological function of MSCs.But the role of exosomes derived from human umbilical cord mesenchymal stem cells(hUC-MSCs)in insulin resistance of human adipocytes is unclear.In this study,exosomes were harvested from the conditioned medium of hUC-MSCs and added to insulin-resistant adipocytes.Insulin-stimulated glucose uptake was measured by glucose oxidase/peroxidase assay.The signal pathway involved in exosome-treated adipocytes was detected by RT-PCR and Western blotting.The biological characteristics and function were compared between hUC-MSCs and human adipose-derived mesenchymal stem cells(hAMSCs).The results showed that hAMSCs had better adipogenic ability than hUC-MSCs.After induction of mature adipocytes by adipogenesis of hAMSC,the model of insulin-resistant adipocytes was successfully established by TNF-αand high glucose intervention.After exosome treatment,the insulin-stimulated glucose uptake was significantly increased.In addition,the effect of exosomes could be stabilized for at least 48 h.Furthermore,the level of leptin was significantly decreased,and the mRNA expression of sirtuin-1 and insulin receptor substrate-1 was significantly upregulated after exosome treatment.In conclusion,exosomes significantly improve insulin sensitivity in insulin-resistant human adipocytes,and the mechanism involves the regulation of adipokines.展开更多
Obesity and the metabolic syndrome are becoming increasingly prevalent not only in adults,but also in adolescents.The metabolic syndrome,a complex cluster of metabolic abnormalities,increases one’s risk of developing...Obesity and the metabolic syndrome are becoming increasingly prevalent not only in adults,but also in adolescents.The metabolic syndrome,a complex cluster of metabolic abnormalities,increases one’s risk of developing type 2 diabetes and cardiovascular disease(CVD).Dyslipidemia,a key component of the metabolic syndrome,is highly associated with insulin resistance and contributes to increased CVD risk.Dyslipidemia has traditionally been assessed using a fasting lipid profile [i.e.fasting triglycerides,total cholesterol,low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)].However,the postprandial state predominates over the course of a day and non-fasting triglycerides independently predict CVD risk.In insulin resistant states,the intestine overproduces triglyceride-rich lipoprotein(TRL) particles,termed chylomicrons(CMs),following ingestion of a fat-containing meal,as well as in the fasting state.Along with elevated hepatic TRLs(i.e.very-low density lipoproteins),CMs contribute to remnant lipoprotein accumulation,small dense LDL particles,and reduced HDL-C,which collectively increase CVD risk.Given the early genesis of atherosclerosis and physiological metabolic changes during adolescence,studying postprandial dyslipidemia in the adolescent population is an important area of study.Postprandial dyslipidemia in the pediatric population poses a significant public health concern,warranting a better understanding of its pathogenesis and association with insulin resistance and CVD.This review discusses the metabolic syndrome,focusing on the link between insulin resistance,postprandial dyslipidemia,and CVD risk.Furthermore,the clinical significance and functional assessment of postprandial dyslipidemia,specifically in the adolescent population,is discussed in more detail.展开更多
Objective: To evaluate the insulin sensitivity action of ferulic acid(FA) in skeletal muscle and hypothalamus of high-fat diet(HFD)-induced obese mice. Methods: Obese mouse model was induced by HFD(45 kcal% lard fat) ...Objective: To evaluate the insulin sensitivity action of ferulic acid(FA) in skeletal muscle and hypothalamus of high-fat diet(HFD)-induced obese mice. Methods: Obese mouse model was induced by HFD(45 kcal% lard fat) for 16 weeks. After 8 weeks of HFD feeding, these obese mice were orally treated with FA at doses of 25 and 50 mg/kg/day for 8 weeks. At the end of all treatments, the epididymal fat, pancreas, skeletal muscle and hypothalamus were removed for biochemical parameter and protein expression examinations. Results: FA treatment significantly decreased leptin level in fat tissue and insulin level in pancreas(P < 0.05). Interestingly, obese mice treated with FA increased the protein expressions of insulin receptor substrate-1, phosphatidylinositol 3-kinase, and phosphorylated-protein kinase B in both muscle and brain(P < 0.05). The phosphorylations of adenosine monophosphate-activated protein kinase and acetyl-CoA carboxylase in muscle, and leptin receptor protein in hypothalamus were also increased(P < 0.05). The pancreatic islets histology showed smaller size in obese mice treated with FA compared to untreated obese mice. Conclusions: These findings indicate the beneficial effect of FA in improving insulin resistance in HFD-induced obese mice. These effects are probably mediated via modulating the insulin receptor substrate/phosphatidylinositol 3-kinase/protein kinase B or adenosine monophosphate-activated protein kinase pathways.展开更多
Objective To investigate the expression of phosphatase and tension homolog(PTEN) in adipose tissue of KKAy diabetic mice, a mouse model of type 2 diabetes. Methods KKAy diabetic mice were fed with high fat diet for 4 ...Objective To investigate the expression of phosphatase and tension homolog(PTEN) in adipose tissue of KKAy diabetic mice, a mouse model of type 2 diabetes. Methods KKAy diabetic mice were fed with high fat diet for 4 weeks. After blood glucose met the criteria of diabetes(over 16.7 mmol/L), mice were randomly divided into 3 groups: a control group(without any treatment), a rosiglitazone group(treated with rosiglitazone 12.5 mg/kg·d once per day), and a metformin group(treated with metformin 3 g/kg·d twice daily). After 4 weeks, we then determined the expression of PTEN and phosphoserine 473-Akt(pS473-Akt) in the epididymal adipose tissue with Western blots. The mice in each group were further divided into the insulin(-) subgroup and insulin(+) subgroup, which were intraperitoneally injected with saline and insulin(5 mU/g body weight), respectively. Results The expression of PTEN was elevated in the epididymal adipose tissue obtained from KKAy diabetic mice compared with that from the C57BL/6J mice(P<0.001). In accordance with the enhanced expression of PTEN, the level of pS473-Akt stimulated by insulin was decreased in the adipose tissue of KKAy mice compared to the C57BL/6J mice(P<0.001). Treatment with the insulin-sensitizing agents, rosiglitazone and metformin did not inhibit the elevated expression of PTEN in adipose tissue of KKAy diabetic mice. Conclusion PTEN may play an important role in the development of insulin resistance in adipose tissue of type 2 diabetes mice model.展开更多
Objective:Research has shown that celastrol can effectively treat a variety of diseases,yet when passing a certain dosage threshold,celastrol becomes toxic,causing complications such as liver and kidney damage and ery...Objective:Research has shown that celastrol can effectively treat a variety of diseases,yet when passing a certain dosage threshold,celastrol becomes toxic,causing complications such as liver and kidney damage and erythrocytopenia,among others.With this dichotomy in mind,it is extremely important to find ways to preserve celastrol’s efficacy while reducing or preventing its toxicity.Methods:In this study,insulin-resistant Hep G2(IR-Hep G2)cells were prepared using palmitic acid and used for in vitro experiments.IR-Hep G2 cells were treated with celastrol alone or in combination with Nacetylcysteine(NAC)or ferrostatin-1(Fer-1)for 12,24 or 48 h,at a range of doses.Cell counting kit-8assay,Western blotting,quantitative reverse transcription-polymerase chain reaction,glucose consumption assessment,and flow cytometry were performed to measure celastrol’s cytotoxicity and whether the cell death was linked to ferroptosis.Results:Celastrol treatment increased lipid oxidation and decreased expression of anti-ferroptosis proteins in IR-Hep G2 cells.Celastrol downregulated glutathione peroxidase 4(GPX4)m RNA.Molecular docking models predicted that solute carrier family 7 member 11(SLC7A11)and GPX4 were covalently bound by celastrol.Importantly,we found for the first time that the application of ferroptosis inhibitors(especially NAC)was able to reduce celastrol’s toxicity while preserving its ability to improve insulin sensitivity in IR-Hep G2 cells.Conclusion:One potential mechanism of celastrol’s cytotoxicity is the induction of ferroptosis,which can be alleviated by treatment with ferroptosis inhibitors.These findings provide a new strategy to block celastrol’s toxicity while preserving its therapeutic effects.展开更多
Simiao Wan(SMW)is a traditional Chinese formula,including Atractylodis Rhizoma,Achyranthis Bidentatae Radix,Phellodendri Chinensis Cortex and Coicis Semen at the ratio of 1:1:2:2.It can be used to the treatment of dia...Simiao Wan(SMW)is a traditional Chinese formula,including Atractylodis Rhizoma,Achyranthis Bidentatae Radix,Phellodendri Chinensis Cortex and Coicis Semen at the ratio of 1:1:2:2.It can be used to the treatment of diabetes.However,its bioactive compounds and underlying mechanism are unclear.This study was designed to screen the antilipolytic fraction from SMW and investigate its therapeutic mechanisms on hepatic insulin resistance.Different fractions of SMW were prepared by membrane separation combined with macroporous resin and their antilipolytic activity was screened in fasted mice.The effects of 60%ethanol elution(ESMW)on lipolysis were investigated in 3T3-L1 adipocytes stimulated by palmitic acid(PA)and high fat diet(HFD)-fed mice.In our study,ESMW was the bioactive fraction responsible for the antilipolytic activity of SMW and 13 compounds were characterized from ESMW by UHPLC-QTOF-MS/MS.ESMW suppressed protein kinase A(PKA)-hormone-sensitive lipase(HSL)related lipolysis and increased AMP-activated protein kinase(AMPK)phosphorylation in PA challenged 3T3-L1 adipocytes.AMPKa knockdown abolished the inhibitory effects of ESMW on IL-6 and HSL pSer-660,revealing that the antilipolytic and anti-inflammatory activities of ESMW are AMPK dependent.Furthermore,ESMW ameliorated insulin resistance and suppressed lipolysis in HFD-fed mice.It inhibited diacylglycerol accumulation in the liver and inhibited hepatic gluconeogenesis.Conditional medium collected from ESMW-treated 3T3-L1 cells ameliorated insulin action on hepatic gluconeogenesis in liver cells,demonstrating that the antilipolytic activity contributed to ESMW beneficial effects on hepatic glucose production.In conclusion,ESMW,as the antilipolytic fraction of SMW,inhibited PKA-HSL related lipolysis by activating AMPK,inhibiting diacylglycerol(DAG)accumulation in the liver and thereby improving insulin resistance and hepatic gluconeogenesis.展开更多
Insulin resistance is one of leading pathogenic process in diabetes mellitus type-2. It is known that high-fructose intake leads to obesity, diabetes, dyslipidemia in rodents. The aim of our study was to evaluate the ...Insulin resistance is one of leading pathogenic process in diabetes mellitus type-2. It is known that high-fructose intake leads to obesity, diabetes, dyslipidemia in rodents. The aim of our study was to evaluate the effect of Blood bumet＇s extract on body weight, visceral fat, blood glucose, plasma insulin, lipid profiles, lipid peroxidation and enzymatic antioxidants （superoxide dismutase, catalase, glutathione reductase） in fructose-induced type-2 diabetic rats. Our results showed that in high-fructose-induced diabetic rats were observed abdominal obesity, hyperglycemia, hyperinsulinemia, increased lipid profiles and atherogenic index, decreased insulin sensitivity, activation of lipid peroxidation and reduced activities of enzymatic antioxidants. Blood bumet＇s extract was able to improve insulin resistance, glucose toleration, rectifies dyslipidemia and abolish the damage in antioxidant system in terms of high-fructose feeding in rats.展开更多
The increasing prevalence of metabolic disorders and neurodegenerative diseases has uncovered shared pathophysiological pathways,with insulin resistance and mitochondrial dysfunction emerging as critical contributors ...The increasing prevalence of metabolic disorders and neurodegenerative diseases has uncovered shared pathophysiological pathways,with insulin resistance and mitochondrial dysfunction emerging as critical contributors to cognitive decline.Insulin resistance impairs neuronal metabolism and synaptic function,fostering neurodegeneration as observed in Alzheimer’s disease and Down syndrome.Indeed,Down syndrome,characterized by the triplication of the APP gene,represents a valuable genetic model for studying early-onset Alzheimer’s disease and accelerated aging.Building on the link between metabolic dysfunctions and neurodegeneration,innovative strategies addressed brain insulin resistance as a key driver of cognitive decline.Intranasal insulin has shown promise in improving cognition in early Alzheimer’s disease and type 2 diabetes,supporting the concept that restoring insulin sensitivity can mitigate neurodegeneration.However,insulin-based therapies risk desensitizing insulin signaling,potentially worsening the disease.Incretins,particularly glucagon-like peptide 1 receptor agonists,offer neuroprotective benefits by enhancing insulin sensitivity,metabolism,and synaptic plasticity while reducing oxidative distress and neuroinflammation.This review focuses on current knowledge on the metabolic and molecular interactions between insulin resistance,mitochondrial dynamics(including their roles in energy metabolism),and oxidative distress regulation,as these are pivotal in both Alzheimer’s disease and Down syndrome.By addressing these interconnected mechanisms,innovative treatments may emerge for both metabolic and neurodegenerative disorders.展开更多
Type 2 diabetes mellitus has central complications:Diabetes,a metabolic disorder primarily characterized by hyperglycemia due to insufficient insulin secretion,or impaired insulin signaling,has significant central com...Type 2 diabetes mellitus has central complications:Diabetes,a metabolic disorder primarily characterized by hyperglycemia due to insufficient insulin secretion,or impaired insulin signaling,has significant central complications.Type 2 diabetes mellitus(T2DM),the most prevalent type of diabetes,affects more than 38 million individuals in the United States(approximately 1 in 10)and is defined by chronic hyperglycemia and insulin resistance,which refers to a reduced cellular response to insulin.展开更多
The shared links between Alzheimer’s disease and type 2 diabetes mellitus:Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2DM)are two prevalent conditions that come with substantial daily struggles.Emerging evi...The shared links between Alzheimer’s disease and type 2 diabetes mellitus:Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2DM)are two prevalent conditions that come with substantial daily struggles.Emerging evidence highlights that these diseases share similar pathophysiological features,including insulin resistance and chronic inflammation,which contribute to their rapid progression(Chen et al.,2022).Insulin resistance,a hallmark of T2DM,has been suggested to exacerbate neurodegeneration in AD.Similarly,chronic low-grade inflammation in T2DM parallels with neuroinflammation,which is observed in AD,suggesting overlapping pathophysiological mechanisms in T2DM and AD.展开更多
Objective To analyze the diagnostic efficacy of lipid-related insulin resistance(IR)markers in patients with non-alcoholic fatty liver disease(NAFLD)and metabolic abnormalities(MA).Method Patients with NAFLD with MA,n...Objective To analyze the diagnostic efficacy of lipid-related insulin resistance(IR)markers in patients with non-alcoholic fatty liver disease(NAFLD)and metabolic abnormalities(MA).Method Patients with NAFLD with MA,non-NAFLD patients with MA,and patients with NAFLD without MA underwent liver biopsy.Homeostasis model assessment of insulin resistance(HOMA-IR),triglyceride/high-density lipoprotein cholesterol(TG/HDL-C),visceral obesity index(VAI),lipid accumulation product(LAP),and triglyceride glucose(TyG)index were analyzed.The diagnostic efficacy of these indicators of NAFLD was also evaluated.Results In the NAFLD-MA group,BMI,HOMA-IR,LAP,VAI,TyG index,and TG/HDL-C ratio were higher than those in the non-NAFLD-MA group(P<0.001).Logistic regression indicated that BMI and TyG index were independent risk factors for NAFLD.Receiver Operating Characteristic(ROC)curves analysis revealed that the Area Under the ROC Curve(AUC)for TyG-BMI was 0.819,and the optimal cutoff for NAFLD was TyG-BMI 39.77.For patients with NAFLD with or without MA,logistic regression analysis suggested that age,TG level,and TyG index were independent risk factors.The area under the ROC curve showed that AUC for the TyG index was 0.724.The optimal cutoff for NAFLD-non MA was a TyG index of 1.580.Conclusion TyG index has diagnostic value in both types of NAFLD;however,TyG-BMI is better in patients with NAFLD with MA and may be an effective screening indicator alone in patients with NAFLD without MA.展开更多
Background Molecular hydrogen, as a novel antioxidant, has been proven effective in treating many diseases. This study aimed to evaluate the therapeutic effects of hydrogen saturated saline in treatment of a rat mode...Background Molecular hydrogen, as a novel antioxidant, has been proven effective in treating many diseases. This study aimed to evaluate the therapeutic effects of hydrogen saturated saline in treatment of a rat model of diabetes mellitus and a rat model of insulin resistant. Methods A rat diabetes mellitus model was established by feeding a high fat/high carbohydrate diet followed by injection of a small dose of streptozotocin, and an insulin resistant model was induced with a high glucose and high fat diet. Hydrogen saturated saline was administered to rats with both models conditions on a daily basis for eight weeks. A pioglitazone-treated group and normal saline-treated group served as positive and negative controls. The general condition, body weight, blood glucose, blood lipids, and serum insulin levels of rats were examined at the 8th week after treatment. The oxidative stress indices, including serum superoxide dismutase （SOD）, glutathione （GSH） and malondialdehyde （MDA） were also evaluated after eight weeks of treatment using the commercial kits.Results Hydrogen saturated saline showed great efficiency in improving the insulin sensitivity and lowering blood glucose and lipids. Meanwhile, the therapeutic effects of hydrogen saturated saline were superior to those of pioglitazone. Hydrogen saturated saline markedly attenuated the MDA level and elevated the levels of antioxidants SOD and GSH. Conclusion Hydrogen saturated saline may improve the insulin resistance and alleviate the symptoms of diabetes mellitus by reducing the oxidative stress and enhancing the anti-oxidant system.展开更多
Objective： To investigate the effects of Huanglian Jiedu Decoction （黄连解毒汤, HLJDD） on glucose transporter 4 （GLUT4） protein expressions in insulin-resistant murine target tissues. Methods： The experimental m...Objective： To investigate the effects of Huanglian Jiedu Decoction （黄连解毒汤, HLJDD） on glucose transporter 4 （GLUT4） protein expressions in insulin-resistant murine target tissues. Methods： The experimental male Wistar rats were established into insulin resistant models by injecting streptozotocin （STZ 30 mg/kg） via caudal vein and feeding them with high fat high caloric diet, and randomly divided into the model group, the aspirin group and the HLJDD group. Besides, a normal group was set up for control. Changes of body weight （BW）, levels of serum fasting blood glucose （FBG）, serum fasting insulin （FINS） and oral glucose tolerance test （OGTT） were routinely determined. The expression of GLUT4 protein in adipose and skeletal muscle tissues before and after insulin stimulation was determined with Western blot. Results： In the HLJDD group after treatment, BW and FBG got decreased, OGTT improved, and the expression and translocation of GLUT4 protein elevated obviously, either before or after insulin stimulation, as compared with those in the model group, showing significant differences respectively. Conclusion： The mechanism of improving insulin resistance by HLJDD is probably associated with its effect in elevating GLUT4 protein expression and translocation in adipose and skeletal muscle tissues of insulin resistant rats.展开更多
Background Under an insulin resistance （IR） state, overproduction of reactive oxygen species （ROS） may be playing a major role in the pathogenesis of endothelial dysfunction, hypertension and atherosclerosis. Rece...Background Under an insulin resistance （IR） state, overproduction of reactive oxygen species （ROS） may be playing a major role in the pathogenesis of endothelial dysfunction, hypertension and atherosclerosis. Recently, increasing attention has been drawn to the beneficial effects of heme oxygenase-1 （HO-1） in the cardiovascular system. This study aimed to investigate the effects of HO-1 on vascular function of thoracic aorta in IR rats and demonstrate the probable mechanisms of HO-1 against endothelial dysfunction in IR states. Methods Sprague-Dawley （SD） rats fed with high-fat diet for 6 weeks and the IR models were validated with hyperinsulinemic-euglycemic clamp test. Then the IR rat models （n=-44） were further randomized into 3 subgroups, namely, the IR control group （n=26, in which 12 were sacrificed immediately and evaluated for all study measures）, a hemin treated IR group （n=-10） and a zinc protoporphyrin-Ⅸ （ZnPP-Ⅸ） treated IR group （n=-8） that were fed with a high-fat diet. Rats with standardized chow diet were used as the normal control group （n=-12）. The rats in IR control group, hemin treated IR group and ZnPP-Ⅸ treated IR group were subsequently treated every other day with an intraperitoneal injection of normal saline, hemin （inducer of HO-1, 30 μmol/kg） or ZnPP-Ⅸ （inhibitor of HO-1, 10 μmol/kg） for 4 weeks. Rats in the normal control group remained on a standardized chow diet and were treated with intraperitoneal injections of normal saline every other day for 4 weeks. Systolic arterial blood pressure （SABP） was measured by tail-cuffed microphotoelectric plethysmography. The blood carbon monoxide （CO） was measured by blood gas analysis. The levels of nitdc oxide （NO）, inducible nitric oxide synthase （iNOS）, endothelial nitric oxide synthase （eNOS）, blood glucose （BG）, insulin, total cholesterol （TC） and triglyceride （TG） in serum, and the levels of total antioxidant capacity （TAOC）, malondialdehyde （MDA） and superoxide dismutase （SOD） in the aorta were measured. The expression of HO-1 mRNA and HO-1 protein in aortal tissue were detected by semi-quantitative RT-PCR and Western blot. The vasoreacUve tensometry was performed with thoracic aortic rings （TARs）. Results Compared with the normal control group, the levels of SABP, BG, insulin, TC, TG, NO, iNOS and MDA were higher, while the levels of CO, TAOC, SOD and eNOS were lower in IR control rats. After treatment of IR rats for 4 weeks a more intensive expression of HO-1 mRNA and HO-1 protein were observed in hemin treated IR group compared with the normal control group. And compared with 4-week IR control rats, the levels of CO, TAOC, SOD and eNOS were increased, while the levels of SABP and iNOS activity were lower in the hemin treated IR group. Administration of hemin in IR rats appeared to improve the disordered vasorelaxation of TARs to acetylcholine （ACh）. Alternatively, the reverse results of SABP, CO, TAOC, SOD, iNOS and vasorelaxation responses to ACh were observed in IR rats with administration of ZnPP-Ⅸ. Conclusions The endothelial dysfunction in the aorta is present in the IR state. The protective effects of HO-1 against aortic endothelial dysfunction may be due to its antioxidation and regulative effect of vasoactive substances. It is proposed that hemin, inducer of HO-1, could be a potential therapeutic option for vascular dysfunction in IR states.展开更多
OBJECTIVE： To explore whether the insulin resis- tance （IR） model could be established through feed- ing Sprague-Dawley （SD） rats high-sugar and high-fat diets and to further observe the preven- tive and treatmen...OBJECTIVE： To explore whether the insulin resis- tance （IR） model could be established through feed- ing Sprague-Dawley （SD） rats high-sugar and high-fat diets and to further observe the preven- tive and treatment effects of different doses of Dan- qidihuang Granules in rats. METHODS： Thirty-two SD rats were divided ran- domly into control group A （given regular feed）, model group B （food high in sugar and fat）, inter- vention group C （food high in sugar and fat as well as regular doses of Danqidihuang Granules）, and in- tervention group D （food high in sugar and fat as well as double doses of Danqidihuang Granules）. The interventions were for 8 weeks. Motion, change in color, body weight, and food intake, as well as plasma lipids （including low-density lipopro- tein-cholesterol （LDL-C）, high-density lipopro- tein-cholesterol （HDL-C）, total cholesterol （TC） and triglyceride （TG）, fasting blood glucose （FBG）, fast-ing insulin （FINs） levels, insulin sensitivity index （ISI）, and insulin resistance index （HOMO-IR） were observed. RESULTS： At the end of the second week of the ex- periment, the appetite and activities of rats in groups B, C and D decreased significantly com- pared with group A. The fur of the rats in those three groups was curly. After the fourth week, the activities, food intake and color of rats in group B were worse than those in groups C and D, but there were no significant differences in weight （P〉0.05）. Compared with group A, LDL-C, TC, FBG and HO- MO-IR in model group 13 were increased significant- ly （P〈0.05）, whereas the FINs and ISI increased obvi- ously （P〈0.05）. The levels of LDL-C and TC in group D was decreased obviously compared with those in group C, and HOMO-IR in group D was less than that in group B CP〈0.05）. CONCLUSION： Danqidihuang Granules helped to prevent and improved the insulin resistance of rats.展开更多
BACKGROUND Acute hyperglycemia due to insulin resistance is common in critically ill patients,typically managed with insulin infusion.However,the occurrence of transient extreme insulin resistance(EIR)requiring except...BACKGROUND Acute hyperglycemia due to insulin resistance is common in critically ill patients,typically managed with insulin infusion.However,the occurrence of transient extreme insulin resistance(EIR)requiring exceptional high-dose insulin is rare.CASE SUMMARY We present the case of a 68-year-old woman with pneumonia who suffered an out-of-hospital cardiac arrest,subsequently developing transient EIR following a new episode of sepsis.Remarkably,insulin resistance rapidly reversed when the insulin infusion rate peaked at 960 units/hour(a total of 18224 units on that day),and it was promptly titrated down to zero upon achieving the target glucose level.CONCLUSION Exceptional high-dose insulin infusion may be required in critically ill patients with stress-related EIR,which is typically transient.Clinicians should be aware of the phenomenon and cautious to avoid hypoglycemia and fluid overload during the steep titration of high-dose insulin infusion.展开更多
Recent studies have potentiated the essential role of androgens in normal follicu-logenesis and,therefore,female fertility.Contrastingly,excess androgen levels,i.e.,hyperandrogenism(HA),a hallmark characteristic of po...Recent studies have potentiated the essential role of androgens in normal follicu-logenesis and,therefore,female fertility.Contrastingly,excess androgen levels,i.e.,hyperandrogenism(HA),a hallmark characteristic of polycystic ovary syndrome,overrides the delicate balance of folliculogenesis,leading to follicular arrest and ovulatory issues.Insulin resistance(IR)has a profound effect on elevating androgen secretion and is considered one of the primary factors driving both ovarian androgen production and metabolic dysfunction in polycystic ovary syndrome.Together with IR,disruptions in key intraovarian and systemic factors,including activin,inhibin,follistatin,anti-Mullerian hormone,bone morpho-genetic proteins,growth differentiation factor-9 and Kit ligand,as well as dysreg-ulation in both the insulin and the transforming growth factor-βsuperfamily signaling pathway,contribute to follicular arrest,elevated androgen levels and metabolic dysfunction,exacerbating HA.Additionally,suppression of sex hormone-binding globulin,disrupted adipose-neuroendocrine signaling and altered microRNA expression heighten HA,with IR serving as the fundamental contributor.Emerging evidence implicates impaired atresia together with non-apoptotic cell death,such as ferroptosis and pyroptosis,which have also been associated with ovarian dysfunction.A comprehensive understanding of the most significant factors,particularly IR,which amplifies androgen production through hyperinsulinemia-mediated stimulation of theca cells,is essential for identifying targeted therapeutic strategies.展开更多
BACKGROUND Tacrolimus(FK506)is a key calcineurin inhibitor used to prevent organ transplant rejection and is effective in improving graft survival.However,it is linked to hyperglycemia and insulin resistance,contribut...BACKGROUND Tacrolimus(FK506)is a key calcineurin inhibitor used to prevent organ transplant rejection and is effective in improving graft survival.However,it is linked to hyperglycemia and insulin resistance,contributing to new-onset diabetes after transplantation and negatively affecting islet function.AIM To study the effects of tacrolimus on the insulin signaling pathway of hepatocytes.METHODS HL7702 cells were treated with different concentrations of tacrolimus(0.1 mg/L,1 mg/L,5 mg/L)for 24 hours.The proteins involved in insulin signaling were detected by Western blotting.RESULTS Compared with the control group,phosphorylation of insulin receptor substrate(IRS)1 at Ser 307 and Ser 323 were increased significantly when the tacrolimus concentration reached 1 and 5 mg/L.Phosphorylation of IRS1 at Ser 1101 was also increased,although not significantly.However,phosphorylation of Ribosomal protein S6 kinase beta-1 at Thr 389 was decreased significantly.The levels of phosphorylated glycogen synthase kinase 3αSer 21 and Ser 9 were increased.Surprisingly,phosphorylation of glycogen synthase at Ser 641 was increased.There was no significant change in the activity of glycogen phosphorylase.CONCLUSION Tacrolimus has no direct effect on hepatic glucose metabolism,but inhibits IRS1-mediated insulin signaling.This may be one of the underlying mechanisms by which tacrolimus induces insulin resistance.展开更多
Type 2 diabetes mellitus and Parkinson's disease are chronic diseases linked to a growing pandemic that affects older adults and causes significant socio-economic burden.Epidemiological data supporting a close rel...Type 2 diabetes mellitus and Parkinson's disease are chronic diseases linked to a growing pandemic that affects older adults and causes significant socio-economic burden.Epidemiological data supporting a close relationship between these two aging-related diseases have resulted in the investigation of shared pathophysiological molecular mechanisms.Impaired insulin signaling in the brain has gained increasing attention during the last decade and has been suggested to contribute to the development of Parkinson's disease through the dysregulation of several pathological processes.The contribution of type 2 diabetes mellitus and insulin resistance in neurodegeneration in Parkinson's disease,with emphasis on brain insulin resistance,is extensively discussed in this article and new therapeutic strategies targeting this pathological link are presented and reviewed.展开更多
基金China National Major Projects(2009ZX09103-436)and 973 Program(2011CB915503)of Science and Technology of P.R.Chinathe reservation-talent project of Yunnan Province(2009CI073)+1 种基金the foundation of study abroad returnees from Ministry of Personnel for financial support(Ms.Li-Xin Yang)the foundations from CAS(Dr.Gang Xu).
文摘Medicinal plants have a long history of use in China to treat diabetic symptoms.Ancient Chinese medical manuscripts and ethnobotanical surveys document plant remedies that continue to be actively used in China for the treatment of diabetic symptoms.Based on a systematic ancient Chinese medical manuscripts review in combination with ethnobotanical survey,16 medicinal plants for the traditional treatment of diabetic symptoms were identified for the evaluation of anti-insulin resistance bioactivity.The biological activity of 16 medicinal plants was tested on dexamethasone(DXMS)-induced insulin resistant HepG2 cells.The result shows that 11 of the 16 medicinal plants enhanced glucose uptake of DXMS-induced insulin resistant HepG2 cells,thereby demonstrating their ability to increase insulin sensitivity,other five medicinal plants including Astragalus membranaceus were found ineffective.The study shows that ancient Chinese medical manuscripts and ethnobotanical surveys on plants for the prevention and treatment of diabetic symptoms provide a promising knowledge base for drug discovery to mitigate the global diabetes epidemic.
基金the grants from National Key Research and Development Program of China(2016YFA0101002)National Key R&D Program of China(2017YFC1309603)National Natural Science Foundation of China(Nos.81170736,81570715,81870579).
文摘Insulin resistance is an essential characteristic of type 2 diabetes mellitus(T2DM),which can be induced by glucotoxicity and adipose chronic inflammation.Mesenchymal stem cells(MSCs)and their exosomes were reported to ameliorate T2DM and its complications by their immunoregulatory and healing abilities.Exosomes derived from MSCs contain abundant molecules to mediate crosstalk between cells and mimic biological function of MSCs.But the role of exosomes derived from human umbilical cord mesenchymal stem cells(hUC-MSCs)in insulin resistance of human adipocytes is unclear.In this study,exosomes were harvested from the conditioned medium of hUC-MSCs and added to insulin-resistant adipocytes.Insulin-stimulated glucose uptake was measured by glucose oxidase/peroxidase assay.The signal pathway involved in exosome-treated adipocytes was detected by RT-PCR and Western blotting.The biological characteristics and function were compared between hUC-MSCs and human adipose-derived mesenchymal stem cells(hAMSCs).The results showed that hAMSCs had better adipogenic ability than hUC-MSCs.After induction of mature adipocytes by adipogenesis of hAMSC,the model of insulin-resistant adipocytes was successfully established by TNF-αand high glucose intervention.After exosome treatment,the insulin-stimulated glucose uptake was significantly increased.In addition,the effect of exosomes could be stabilized for at least 48 h.Furthermore,the level of leptin was significantly decreased,and the mRNA expression of sirtuin-1 and insulin receptor substrate-1 was significantly upregulated after exosome treatment.In conclusion,exosomes significantly improve insulin sensitivity in insulin-resistant human adipocytes,and the mechanism involves the regulation of adipokines.
文摘Obesity and the metabolic syndrome are becoming increasingly prevalent not only in adults,but also in adolescents.The metabolic syndrome,a complex cluster of metabolic abnormalities,increases one’s risk of developing type 2 diabetes and cardiovascular disease(CVD).Dyslipidemia,a key component of the metabolic syndrome,is highly associated with insulin resistance and contributes to increased CVD risk.Dyslipidemia has traditionally been assessed using a fasting lipid profile [i.e.fasting triglycerides,total cholesterol,low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)].However,the postprandial state predominates over the course of a day and non-fasting triglycerides independently predict CVD risk.In insulin resistant states,the intestine overproduces triglyceride-rich lipoprotein(TRL) particles,termed chylomicrons(CMs),following ingestion of a fat-containing meal,as well as in the fasting state.Along with elevated hepatic TRLs(i.e.very-low density lipoproteins),CMs contribute to remnant lipoprotein accumulation,small dense LDL particles,and reduced HDL-C,which collectively increase CVD risk.Given the early genesis of atherosclerosis and physiological metabolic changes during adolescence,studying postprandial dyslipidemia in the adolescent population is an important area of study.Postprandial dyslipidemia in the pediatric population poses a significant public health concern,warranting a better understanding of its pathogenesis and association with insulin resistance and CVD.This review discusses the metabolic syndrome,focusing on the link between insulin resistance,postprandial dyslipidemia,and CVD risk.Furthermore,the clinical significance and functional assessment of postprandial dyslipidemia,specifically in the adolescent population,is discussed in more detail.
基金supported by the Faculty of Medicine Research Fund(GEN2-01/2016),Thammasat University,Thailand
文摘Objective: To evaluate the insulin sensitivity action of ferulic acid(FA) in skeletal muscle and hypothalamus of high-fat diet(HFD)-induced obese mice. Methods: Obese mouse model was induced by HFD(45 kcal% lard fat) for 16 weeks. After 8 weeks of HFD feeding, these obese mice were orally treated with FA at doses of 25 and 50 mg/kg/day for 8 weeks. At the end of all treatments, the epididymal fat, pancreas, skeletal muscle and hypothalamus were removed for biochemical parameter and protein expression examinations. Results: FA treatment significantly decreased leptin level in fat tissue and insulin level in pancreas(P < 0.05). Interestingly, obese mice treated with FA increased the protein expressions of insulin receptor substrate-1, phosphatidylinositol 3-kinase, and phosphorylated-protein kinase B in both muscle and brain(P < 0.05). The phosphorylations of adenosine monophosphate-activated protein kinase and acetyl-CoA carboxylase in muscle, and leptin receptor protein in hypothalamus were also increased(P < 0.05). The pancreatic islets histology showed smaller size in obese mice treated with FA compared to untreated obese mice. Conclusions: These findings indicate the beneficial effect of FA in improving insulin resistance in HFD-induced obese mice. These effects are probably mediated via modulating the insulin receptor substrate/phosphatidylinositol 3-kinase/protein kinase B or adenosine monophosphate-activated protein kinase pathways.
基金Supported by National Natural Science Foundation of China(81270878)National Key Program of Clinical Science of China(WBYZ2011-873)
文摘Objective To investigate the expression of phosphatase and tension homolog(PTEN) in adipose tissue of KKAy diabetic mice, a mouse model of type 2 diabetes. Methods KKAy diabetic mice were fed with high fat diet for 4 weeks. After blood glucose met the criteria of diabetes(over 16.7 mmol/L), mice were randomly divided into 3 groups: a control group(without any treatment), a rosiglitazone group(treated with rosiglitazone 12.5 mg/kg·d once per day), and a metformin group(treated with metformin 3 g/kg·d twice daily). After 4 weeks, we then determined the expression of PTEN and phosphoserine 473-Akt(pS473-Akt) in the epididymal adipose tissue with Western blots. The mice in each group were further divided into the insulin(-) subgroup and insulin(+) subgroup, which were intraperitoneally injected with saline and insulin(5 mU/g body weight), respectively. Results The expression of PTEN was elevated in the epididymal adipose tissue obtained from KKAy diabetic mice compared with that from the C57BL/6J mice(P<0.001). In accordance with the enhanced expression of PTEN, the level of pS473-Akt stimulated by insulin was decreased in the adipose tissue of KKAy mice compared to the C57BL/6J mice(P<0.001). Treatment with the insulin-sensitizing agents, rosiglitazone and metformin did not inhibit the elevated expression of PTEN in adipose tissue of KKAy diabetic mice. Conclusion PTEN may play an important role in the development of insulin resistance in adipose tissue of type 2 diabetes mice model.
文摘Objective:Research has shown that celastrol can effectively treat a variety of diseases,yet when passing a certain dosage threshold,celastrol becomes toxic,causing complications such as liver and kidney damage and erythrocytopenia,among others.With this dichotomy in mind,it is extremely important to find ways to preserve celastrol’s efficacy while reducing or preventing its toxicity.Methods:In this study,insulin-resistant Hep G2(IR-Hep G2)cells were prepared using palmitic acid and used for in vitro experiments.IR-Hep G2 cells were treated with celastrol alone or in combination with Nacetylcysteine(NAC)or ferrostatin-1(Fer-1)for 12,24 or 48 h,at a range of doses.Cell counting kit-8assay,Western blotting,quantitative reverse transcription-polymerase chain reaction,glucose consumption assessment,and flow cytometry were performed to measure celastrol’s cytotoxicity and whether the cell death was linked to ferroptosis.Results:Celastrol treatment increased lipid oxidation and decreased expression of anti-ferroptosis proteins in IR-Hep G2 cells.Celastrol downregulated glutathione peroxidase 4(GPX4)m RNA.Molecular docking models predicted that solute carrier family 7 member 11(SLC7A11)and GPX4 were covalently bound by celastrol.Importantly,we found for the first time that the application of ferroptosis inhibitors(especially NAC)was able to reduce celastrol’s toxicity while preserving its ability to improve insulin sensitivity in IR-Hep G2 cells.Conclusion:One potential mechanism of celastrol’s cytotoxicity is the induction of ferroptosis,which can be alleviated by treatment with ferroptosis inhibitors.These findings provide a new strategy to block celastrol’s toxicity while preserving its therapeutic effects.
基金supported by the National Key R&D Program of China(Nos.2018YFC1704500 and 2018YFC 1704503)the National Natural Science Foundation of China(Nos.82074080 and 81773877)the Natural Science Foundation of Jiangsu Province(No.BK20181328).
文摘Simiao Wan(SMW)is a traditional Chinese formula,including Atractylodis Rhizoma,Achyranthis Bidentatae Radix,Phellodendri Chinensis Cortex and Coicis Semen at the ratio of 1:1:2:2.It can be used to the treatment of diabetes.However,its bioactive compounds and underlying mechanism are unclear.This study was designed to screen the antilipolytic fraction from SMW and investigate its therapeutic mechanisms on hepatic insulin resistance.Different fractions of SMW were prepared by membrane separation combined with macroporous resin and their antilipolytic activity was screened in fasted mice.The effects of 60%ethanol elution(ESMW)on lipolysis were investigated in 3T3-L1 adipocytes stimulated by palmitic acid(PA)and high fat diet(HFD)-fed mice.In our study,ESMW was the bioactive fraction responsible for the antilipolytic activity of SMW and 13 compounds were characterized from ESMW by UHPLC-QTOF-MS/MS.ESMW suppressed protein kinase A(PKA)-hormone-sensitive lipase(HSL)related lipolysis and increased AMP-activated protein kinase(AMPK)phosphorylation in PA challenged 3T3-L1 adipocytes.AMPKa knockdown abolished the inhibitory effects of ESMW on IL-6 and HSL pSer-660,revealing that the antilipolytic and anti-inflammatory activities of ESMW are AMPK dependent.Furthermore,ESMW ameliorated insulin resistance and suppressed lipolysis in HFD-fed mice.It inhibited diacylglycerol accumulation in the liver and inhibited hepatic gluconeogenesis.Conditional medium collected from ESMW-treated 3T3-L1 cells ameliorated insulin action on hepatic gluconeogenesis in liver cells,demonstrating that the antilipolytic activity contributed to ESMW beneficial effects on hepatic glucose production.In conclusion,ESMW,as the antilipolytic fraction of SMW,inhibited PKA-HSL related lipolysis by activating AMPK,inhibiting diacylglycerol(DAG)accumulation in the liver and thereby improving insulin resistance and hepatic gluconeogenesis.
文摘Insulin resistance is one of leading pathogenic process in diabetes mellitus type-2. It is known that high-fructose intake leads to obesity, diabetes, dyslipidemia in rodents. The aim of our study was to evaluate the effect of Blood bumet＇s extract on body weight, visceral fat, blood glucose, plasma insulin, lipid profiles, lipid peroxidation and enzymatic antioxidants （superoxide dismutase, catalase, glutathione reductase） in fructose-induced type-2 diabetic rats. Our results showed that in high-fructose-induced diabetic rats were observed abdominal obesity, hyperglycemia, hyperinsulinemia, increased lipid profiles and atherogenic index, decreased insulin sensitivity, activation of lipid peroxidation and reduced activities of enzymatic antioxidants. Blood bumet＇s extract was able to improve insulin resistance, glucose toleration, rectifies dyslipidemia and abolish the damage in antioxidant system in terms of high-fructose feeding in rats.
基金supported by Fondi Ateneo grants funded by Sapienza University (#RM120172A3160B53) to EBfunds from Jerome-Lejeune Foundation (#1887-2019b) to EBthe European Union–Next Generation EU (Project ECS 0000024Rome Technopole,–CUP B83C22002820006, NRPMission 4 Component 2 Investment 1.5 to LRR)
文摘The increasing prevalence of metabolic disorders and neurodegenerative diseases has uncovered shared pathophysiological pathways,with insulin resistance and mitochondrial dysfunction emerging as critical contributors to cognitive decline.Insulin resistance impairs neuronal metabolism and synaptic function,fostering neurodegeneration as observed in Alzheimer’s disease and Down syndrome.Indeed,Down syndrome,characterized by the triplication of the APP gene,represents a valuable genetic model for studying early-onset Alzheimer’s disease and accelerated aging.Building on the link between metabolic dysfunctions and neurodegeneration,innovative strategies addressed brain insulin resistance as a key driver of cognitive decline.Intranasal insulin has shown promise in improving cognition in early Alzheimer’s disease and type 2 diabetes,supporting the concept that restoring insulin sensitivity can mitigate neurodegeneration.However,insulin-based therapies risk desensitizing insulin signaling,potentially worsening the disease.Incretins,particularly glucagon-like peptide 1 receptor agonists,offer neuroprotective benefits by enhancing insulin sensitivity,metabolism,and synaptic plasticity while reducing oxidative distress and neuroinflammation.This review focuses on current knowledge on the metabolic and molecular interactions between insulin resistance,mitochondrial dynamics(including their roles in energy metabolism),and oxidative distress regulation,as these are pivotal in both Alzheimer’s disease and Down syndrome.By addressing these interconnected mechanisms,innovative treatments may emerge for both metabolic and neurodegenerative disorders.
基金supported by grants from NIH T32(DK007260,to WC)the Steno North American Fellowship awarded by the Novo Nordisk Foundation(NNF23OC0087108,to WC)+6 种基金STI2030-Major Projects(2021ZD0202700,to HY)the National Natural Science Foundation of China(32241004,to HY)the Natural Science Foundation of Zhejiang Province of China(LR24C090001,to HY)Key R&D Program of Zhejiang Province(2024SSYS0017,to HY)CAMS Innovation Fund for Medical Sciences(2019-12M-5-057,to HY)Fundamental Research Funds for the Central Universities(226-2022-00193,to HY)the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2023-PT310-01,to HY)。
文摘Type 2 diabetes mellitus has central complications:Diabetes,a metabolic disorder primarily characterized by hyperglycemia due to insufficient insulin secretion,or impaired insulin signaling,has significant central complications.Type 2 diabetes mellitus(T2DM),the most prevalent type of diabetes,affects more than 38 million individuals in the United States(approximately 1 in 10)and is defined by chronic hyperglycemia and insulin resistance,which refers to a reduced cellular response to insulin.
基金supported by grants from NIH T32(DK007260,to WC)the Steno North American Fellowship awarded by the Novo Nordisk Foundation(NNF23OC0087108,to WC).
文摘The shared links between Alzheimer’s disease and type 2 diabetes mellitus:Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2DM)are two prevalent conditions that come with substantial daily struggles.Emerging evidence highlights that these diseases share similar pathophysiological features,including insulin resistance and chronic inflammation,which contribute to their rapid progression(Chen et al.,2022).Insulin resistance,a hallmark of T2DM,has been suggested to exacerbate neurodegeneration in AD.Similarly,chronic low-grade inflammation in T2DM parallels with neuroinflammation,which is observed in AD,suggesting overlapping pathophysiological mechanisms in T2DM and AD.
基金Beijing Research Ward Excellence Program(BRWEP2024W102170101)The National Key Research and Development Program(2022YFC2603500,2022YFC2603505)+5 种基金Beijing Municipal Health Commission high-level public health technical personnel construction project(discipline leader-03-26,discipline backbone-02-28)Capital’s Funds for Health Improvement and Research(2022-1-2172)Beijing Hospitals Authority Clinical medicine Development of special funding support(ZLRK202301)Beijing Hospitals Authority"peak"talent training program(DFL20241803)National Key Research and Development Program of China(2023YFC2306900)National Key Research and Development Program of Ministry of Science and Technology(2023YFC2308105).
文摘Objective To analyze the diagnostic efficacy of lipid-related insulin resistance(IR)markers in patients with non-alcoholic fatty liver disease(NAFLD)and metabolic abnormalities(MA).Method Patients with NAFLD with MA,non-NAFLD patients with MA,and patients with NAFLD without MA underwent liver biopsy.Homeostasis model assessment of insulin resistance(HOMA-IR),triglyceride/high-density lipoprotein cholesterol(TG/HDL-C),visceral obesity index(VAI),lipid accumulation product(LAP),and triglyceride glucose(TyG)index were analyzed.The diagnostic efficacy of these indicators of NAFLD was also evaluated.Results In the NAFLD-MA group,BMI,HOMA-IR,LAP,VAI,TyG index,and TG/HDL-C ratio were higher than those in the non-NAFLD-MA group(P<0.001).Logistic regression indicated that BMI and TyG index were independent risk factors for NAFLD.Receiver Operating Characteristic(ROC)curves analysis revealed that the Area Under the ROC Curve(AUC)for TyG-BMI was 0.819,and the optimal cutoff for NAFLD was TyG-BMI 39.77.For patients with NAFLD with or without MA,logistic regression analysis suggested that age,TG level,and TyG index were independent risk factors.The area under the ROC curve showed that AUC for the TyG index was 0.724.The optimal cutoff for NAFLD-non MA was a TyG index of 1.580.Conclusion TyG index has diagnostic value in both types of NAFLD;however,TyG-BMI is better in patients with NAFLD with MA and may be an effective screening indicator alone in patients with NAFLD without MA.
基金This study was supported by the Natural Science Foundation of Shanghai （No. 09ZR1400700）.
文摘Background Molecular hydrogen, as a novel antioxidant, has been proven effective in treating many diseases. This study aimed to evaluate the therapeutic effects of hydrogen saturated saline in treatment of a rat model of diabetes mellitus and a rat model of insulin resistant. Methods A rat diabetes mellitus model was established by feeding a high fat/high carbohydrate diet followed by injection of a small dose of streptozotocin, and an insulin resistant model was induced with a high glucose and high fat diet. Hydrogen saturated saline was administered to rats with both models conditions on a daily basis for eight weeks. A pioglitazone-treated group and normal saline-treated group served as positive and negative controls. The general condition, body weight, blood glucose, blood lipids, and serum insulin levels of rats were examined at the 8th week after treatment. The oxidative stress indices, including serum superoxide dismutase （SOD）, glutathione （GSH） and malondialdehyde （MDA） were also evaluated after eight weeks of treatment using the commercial kits.Results Hydrogen saturated saline showed great efficiency in improving the insulin sensitivity and lowering blood glucose and lipids. Meanwhile, the therapeutic effects of hydrogen saturated saline were superior to those of pioglitazone. Hydrogen saturated saline markedly attenuated the MDA level and elevated the levels of antioxidants SOD and GSH. Conclusion Hydrogen saturated saline may improve the insulin resistance and alleviate the symptoms of diabetes mellitus by reducing the oxidative stress and enhancing the anti-oxidant system.
基金National Natural Science Foundation of P. R. China (No. 30371816)Specialized Research Fund for the Doctoral Program of Higher Education (No. 20030487008)
文摘Objective： To investigate the effects of Huanglian Jiedu Decoction （黄连解毒汤, HLJDD） on glucose transporter 4 （GLUT4） protein expressions in insulin-resistant murine target tissues. Methods： The experimental male Wistar rats were established into insulin resistant models by injecting streptozotocin （STZ 30 mg/kg） via caudal vein and feeding them with high fat high caloric diet, and randomly divided into the model group, the aspirin group and the HLJDD group. Besides, a normal group was set up for control. Changes of body weight （BW）, levels of serum fasting blood glucose （FBG）, serum fasting insulin （FINS） and oral glucose tolerance test （OGTT） were routinely determined. The expression of GLUT4 protein in adipose and skeletal muscle tissues before and after insulin stimulation was determined with Western blot. Results： In the HLJDD group after treatment, BW and FBG got decreased, OGTT improved, and the expression and translocation of GLUT4 protein elevated obviously, either before or after insulin stimulation, as compared with those in the model group, showing significant differences respectively. Conclusion： The mechanism of improving insulin resistance by HLJDD is probably associated with its effect in elevating GLUT4 protein expression and translocation in adipose and skeletal muscle tissues of insulin resistant rats.
文摘Background Under an insulin resistance （IR） state, overproduction of reactive oxygen species （ROS） may be playing a major role in the pathogenesis of endothelial dysfunction, hypertension and atherosclerosis. Recently, increasing attention has been drawn to the beneficial effects of heme oxygenase-1 （HO-1） in the cardiovascular system. This study aimed to investigate the effects of HO-1 on vascular function of thoracic aorta in IR rats and demonstrate the probable mechanisms of HO-1 against endothelial dysfunction in IR states. Methods Sprague-Dawley （SD） rats fed with high-fat diet for 6 weeks and the IR models were validated with hyperinsulinemic-euglycemic clamp test. Then the IR rat models （n=-44） were further randomized into 3 subgroups, namely, the IR control group （n=26, in which 12 were sacrificed immediately and evaluated for all study measures）, a hemin treated IR group （n=-10） and a zinc protoporphyrin-Ⅸ （ZnPP-Ⅸ） treated IR group （n=-8） that were fed with a high-fat diet. Rats with standardized chow diet were used as the normal control group （n=-12）. The rats in IR control group, hemin treated IR group and ZnPP-Ⅸ treated IR group were subsequently treated every other day with an intraperitoneal injection of normal saline, hemin （inducer of HO-1, 30 μmol/kg） or ZnPP-Ⅸ （inhibitor of HO-1, 10 μmol/kg） for 4 weeks. Rats in the normal control group remained on a standardized chow diet and were treated with intraperitoneal injections of normal saline every other day for 4 weeks. Systolic arterial blood pressure （SABP） was measured by tail-cuffed microphotoelectric plethysmography. The blood carbon monoxide （CO） was measured by blood gas analysis. The levels of nitdc oxide （NO）, inducible nitric oxide synthase （iNOS）, endothelial nitric oxide synthase （eNOS）, blood glucose （BG）, insulin, total cholesterol （TC） and triglyceride （TG） in serum, and the levels of total antioxidant capacity （TAOC）, malondialdehyde （MDA） and superoxide dismutase （SOD） in the aorta were measured. The expression of HO-1 mRNA and HO-1 protein in aortal tissue were detected by semi-quantitative RT-PCR and Western blot. The vasoreacUve tensometry was performed with thoracic aortic rings （TARs）. Results Compared with the normal control group, the levels of SABP, BG, insulin, TC, TG, NO, iNOS and MDA were higher, while the levels of CO, TAOC, SOD and eNOS were lower in IR control rats. After treatment of IR rats for 4 weeks a more intensive expression of HO-1 mRNA and HO-1 protein were observed in hemin treated IR group compared with the normal control group. And compared with 4-week IR control rats, the levels of CO, TAOC, SOD and eNOS were increased, while the levels of SABP and iNOS activity were lower in the hemin treated IR group. Administration of hemin in IR rats appeared to improve the disordered vasorelaxation of TARs to acetylcholine （ACh）. Alternatively, the reverse results of SABP, CO, TAOC, SOD, iNOS and vasorelaxation responses to ACh were observed in IR rats with administration of ZnPP-Ⅸ. Conclusions The endothelial dysfunction in the aorta is present in the IR state. The protective effects of HO-1 against aortic endothelial dysfunction may be due to its antioxidation and regulative effect of vasoactive substances. It is proposed that hemin, inducer of HO-1, could be a potential therapeutic option for vascular dysfunction in IR states.
文摘OBJECTIVE： To explore whether the insulin resis- tance （IR） model could be established through feed- ing Sprague-Dawley （SD） rats high-sugar and high-fat diets and to further observe the preven- tive and treatment effects of different doses of Dan- qidihuang Granules in rats. METHODS： Thirty-two SD rats were divided ran- domly into control group A （given regular feed）, model group B （food high in sugar and fat）, inter- vention group C （food high in sugar and fat as well as regular doses of Danqidihuang Granules）, and in- tervention group D （food high in sugar and fat as well as double doses of Danqidihuang Granules）. The interventions were for 8 weeks. Motion, change in color, body weight, and food intake, as well as plasma lipids （including low-density lipopro- tein-cholesterol （LDL-C）, high-density lipopro- tein-cholesterol （HDL-C）, total cholesterol （TC） and triglyceride （TG）, fasting blood glucose （FBG）, fast-ing insulin （FINs） levels, insulin sensitivity index （ISI）, and insulin resistance index （HOMO-IR） were observed. RESULTS： At the end of the second week of the ex- periment, the appetite and activities of rats in groups B, C and D decreased significantly com- pared with group A. The fur of the rats in those three groups was curly. After the fourth week, the activities, food intake and color of rats in group B were worse than those in groups C and D, but there were no significant differences in weight （P〉0.05）. Compared with group A, LDL-C, TC, FBG and HO- MO-IR in model group 13 were increased significant- ly （P〈0.05）, whereas the FINs and ISI increased obvi- ously （P〈0.05）. The levels of LDL-C and TC in group D was decreased obviously compared with those in group C, and HOMO-IR in group D was less than that in group B CP〈0.05）. CONCLUSION： Danqidihuang Granules helped to prevent and improved the insulin resistance of rats.
文摘BACKGROUND Acute hyperglycemia due to insulin resistance is common in critically ill patients,typically managed with insulin infusion.However,the occurrence of transient extreme insulin resistance(EIR)requiring exceptional high-dose insulin is rare.CASE SUMMARY We present the case of a 68-year-old woman with pneumonia who suffered an out-of-hospital cardiac arrest,subsequently developing transient EIR following a new episode of sepsis.Remarkably,insulin resistance rapidly reversed when the insulin infusion rate peaked at 960 units/hour(a total of 18224 units on that day),and it was promptly titrated down to zero upon achieving the target glucose level.CONCLUSION Exceptional high-dose insulin infusion may be required in critically ill patients with stress-related EIR,which is typically transient.Clinicians should be aware of the phenomenon and cautious to avoid hypoglycemia and fluid overload during the steep titration of high-dose insulin infusion.
基金Supported by Incentive Funding for Rated Researchers from the National Research Foundation,Pretoria,No.145943Research Reward from the Research Office of the University of KwaZulu-Natal,Durban,South Africa.
文摘Recent studies have potentiated the essential role of androgens in normal follicu-logenesis and,therefore,female fertility.Contrastingly,excess androgen levels,i.e.,hyperandrogenism(HA),a hallmark characteristic of polycystic ovary syndrome,overrides the delicate balance of folliculogenesis,leading to follicular arrest and ovulatory issues.Insulin resistance(IR)has a profound effect on elevating androgen secretion and is considered one of the primary factors driving both ovarian androgen production and metabolic dysfunction in polycystic ovary syndrome.Together with IR,disruptions in key intraovarian and systemic factors,including activin,inhibin,follistatin,anti-Mullerian hormone,bone morpho-genetic proteins,growth differentiation factor-9 and Kit ligand,as well as dysreg-ulation in both the insulin and the transforming growth factor-βsuperfamily signaling pathway,contribute to follicular arrest,elevated androgen levels and metabolic dysfunction,exacerbating HA.Additionally,suppression of sex hormone-binding globulin,disrupted adipose-neuroendocrine signaling and altered microRNA expression heighten HA,with IR serving as the fundamental contributor.Emerging evidence implicates impaired atresia together with non-apoptotic cell death,such as ferroptosis and pyroptosis,which have also been associated with ovarian dysfunction.A comprehensive understanding of the most significant factors,particularly IR,which amplifies androgen production through hyperinsulinemia-mediated stimulation of theca cells,is essential for identifying targeted therapeutic strategies.
文摘BACKGROUND Tacrolimus(FK506)is a key calcineurin inhibitor used to prevent organ transplant rejection and is effective in improving graft survival.However,it is linked to hyperglycemia and insulin resistance,contributing to new-onset diabetes after transplantation and negatively affecting islet function.AIM To study the effects of tacrolimus on the insulin signaling pathway of hepatocytes.METHODS HL7702 cells were treated with different concentrations of tacrolimus(0.1 mg/L,1 mg/L,5 mg/L)for 24 hours.The proteins involved in insulin signaling were detected by Western blotting.RESULTS Compared with the control group,phosphorylation of insulin receptor substrate(IRS)1 at Ser 307 and Ser 323 were increased significantly when the tacrolimus concentration reached 1 and 5 mg/L.Phosphorylation of IRS1 at Ser 1101 was also increased,although not significantly.However,phosphorylation of Ribosomal protein S6 kinase beta-1 at Thr 389 was decreased significantly.The levels of phosphorylated glycogen synthase kinase 3αSer 21 and Ser 9 were increased.Surprisingly,phosphorylation of glycogen synthase at Ser 641 was increased.There was no significant change in the activity of glycogen phosphorylase.CONCLUSION Tacrolimus has no direct effect on hepatic glucose metabolism,but inhibits IRS1-mediated insulin signaling.This may be one of the underlying mechanisms by which tacrolimus induces insulin resistance.
基金support from Region Stockholm,ALF-project(FoUI-960041)Open Access funding is provided by Karolinska Institute(both to IM)。
文摘Type 2 diabetes mellitus and Parkinson's disease are chronic diseases linked to a growing pandemic that affects older adults and causes significant socio-economic burden.Epidemiological data supporting a close relationship between these two aging-related diseases have resulted in the investigation of shared pathophysiological molecular mechanisms.Impaired insulin signaling in the brain has gained increasing attention during the last decade and has been suggested to contribute to the development of Parkinson's disease through the dysregulation of several pathological processes.The contribution of type 2 diabetes mellitus and insulin resistance in neurodegeneration in Parkinson's disease,with emphasis on brain insulin resistance,is extensively discussed in this article and new therapeutic strategies targeting this pathological link are presented and reviewed.
