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
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
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
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
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
OBJECTIVE To explore hypoglycemic effect of 95%ethanol fraction of Nitraria roborowskii Kom(NRK-C)and its possible mechanism evaluated in the type 2 diabetes mellitus(T2DM)mice.METHODS The body weight,organ indices,bl...OBJECTIVE To explore hypoglycemic effect of 95%ethanol fraction of Nitraria roborowskii Kom(NRK-C)and its possible mechanism evaluated in the type 2 diabetes mellitus(T2DM)mice.METHODS The body weight,organ indices,blood glucose levels,serum biochemical indexes,as well as HE/PAS histopathological section were all analyzed to assess the hypoglycemic effect of NRK-C in T2DM mice induced by a high-fat diet(HFD)combined with six intraperitoneal injections of 35 mg·kg^(-1)of streptozotocin(STZ).The Western blotting and immunofluorescence were further applied to determine the regulatory effect of NRK-C on key signaling proteins.RESULTS The fasting blood glucose levels were significantly reduced after 7 weeks of administration of NRK-C.In addition,NRK-C could also significantly improve glucose tolerance,hepatic glycogen levels,and lipid levels(total cholesterol,triglyceride,low density lipoprotein and high density lipoprotein),and significantly reduced insulin resistance of diabetic mice,which played an important role in the antidiabetic effects.Further mechanism research demonstrated that phosphorylated PI3K expression was up-regulated and p-GSK3βexpression was up-regulated after NRK-C intervention,indicating that NRK-C might exert a potential antidiabetic effect by modulating the PI3K/AKT signaling pathway.CONCLUSION All these results suggested that NRK-C might improve T2DM and had the potential to be used as an adjunctive therapy.展开更多
This editorial discusses the findings of Elbarky et al on the role of selenoprotein P1(SEPP1)in pediatric obesity and insulin resistance.Their study uncovered si-gnificantly lower SEPP1 Levels in children who were obe...This editorial discusses the findings of Elbarky et al on the role of selenoprotein P1(SEPP1)in pediatric obesity and insulin resistance.Their study uncovered si-gnificantly lower SEPP1 Levels in children who were obese compared with hea-lthy peers,demonstrating a negative correlation between SEPP1 levels and mea-sures of adiposity and insulin resistance.These findings suggest that SEPP1 is a biomarker useful in the early identification of insulin resistance in pediatric populations.This editorial emphasizes the clinical implications of the study and calls for further research to validate and explore the role of SEPP1 in metabolic health.展开更多
Insulin resistance(IR)is widely recognized as a key contributor to metabolic disorders,and various surrogate indices have been developed to estimate IR in clinical and research settings.The hyperinsulinemic-euglycemic...Insulin resistance(IR)is widely recognized as a key contributor to metabolic disorders,and various surrogate indices have been developed to estimate IR in clinical and research settings.The hyperinsulinemic-euglycemic clamp is considered the gold standard method for assessing insulin resistance due to its precision;however,its complexity limits its widespread clinical application.Consequently,surrogate indices derived from fasting and post-load glucose and insulin levels have been developed to estimate IR,facilitating early detection and risk stratification in metabolic disorders.This mini-review discusses the clinical utility,strengths,and limitations of key IR indices,including the homeostasis model assessment of IR,quantitative insulin sensitivity check index,Matsuda index,and triglyceride-glucose index.Overall,the evidence presented to date suggests that these indices provide valuable estimates of IR in various popula-tions.Yet,their applicability varies depending on ethnic background,disease status,and clinical setting.Integrating these indices into routine clinical practice and research could improve metabolic risk assessment and guide preventive interventions.Further investigations are necessary to refine their accuracy and determine optimal cut-off values for various populations.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 Cardiovascular disease represents a major complication in patients with type 2 diabetes mellitus(T2DM),with insulin resistance(IR)recognized as a key underlying pathophysiological mechanism.The metabolic sc...BACKGROUND Cardiovascular disease represents a major complication in patients with type 2 diabetes mellitus(T2DM),with insulin resistance(IR)recognized as a key underlying pathophysiological mechanism.The metabolic score for IR(METS-IR),a simple,non-invasive,and insulin-independent surrogate marker of IR,has been validated for risk stratification and prognostic assessment in conditions such as hypertension,ischemic cardiomyopathy,and T2DM.Monitoring fluctuations in METS-IR levels among individuals with T2DM may facilitate early identification of elevated cardiovascular risk and inform timely therapeutic adjustments.AIM To investigate the association between METS-IR and cardiovascular risk in patients with T2DM and to evaluate its potential utility as a predictive biomarker.METHODS This study represents a secondary analysis of a multicenter randomized controlled trial,ultimately including 10191 patients with T2DM aged 40 years to 79 years,with a follow-up duration of approximately 10 years.Baseline METS-IR was calculated using triglycerides,body mass index,high-density lipoprotein cholesterol and fasting plasma glucose.The predictive value of METS-IR for major adverse cardiovascular events(MACEs),all-cause mortality,congestive heart failure,and major coronary heart disease events,was assessed using Cox proportional hazards models,restricted cubic spline analysis,and stratified subgroup analyses.Multivariable adjustments were performed to account for potential confounding factors.RESULTS The incidence of MACEs increased steadily across higher METS-IR quartiles.After adjusting for multiple confounding factors,hazard ratios comparing the highest to the lowest METS-IR quartile were 1.25[95%confidence interval(CI):1.08-1.45]for MACEs,1.55(95%CI:1.23-1.96)for cardiovascular death,1.39(95%CI:1.21-1.59)for allcause mortality,2.22(95%CI:1.74-2.82)for congestive heart failure,and 1.35(95%CI:1.17-1.56)for major coronary heart disease.Restricted cubic spline analysis supported a positive,dose-dependent relationship between rising METS-IR levels and cardiovascular risk.Moreover,adding METS-IR to conventional risk prediction models enhanced their performance,as evidenced by improvements in the C-statistic,net reclassification improvement,and integrated discrimination improvement.Subgroup analyses indicated possible interactions between METS-IR,hemoglobin A1c levels,and aspirin therapy.CONCLUSION METS-IR shows a strong correlation with cardiovascular risk in individuals with T2DM.Tracking METS-IR levels could enhance risk assessment and the prediction of cardiovascular events.展开更多
Objective This study aimed to investigate the association between insulin resistance and the risk of cardiovascular disease.Methods A cross-sectional study including 2128 participants aged 40-79 years was conducted us...Objective This study aimed to investigate the association between insulin resistance and the risk of cardiovascular disease.Methods A cross-sectional study including 2128 participants aged 40-79 years was conducted using data from the National Health and Nutrition Examination Survey from 1999 to 2018.The quantitative insulin sensitivity check index(QUICKI)and homeostasis model assessment ofβ-cell function(HOMA-β)were used as independent variables.The 10-year risk of a first hard atherosclerotic cardiovascular event was used as the dependent variable,with other potential confounding factors considered.Multivariate linear regression models and smooth curve fitting were used to assess the associations between insulin resistance and 10-year risk.Results A total of 2128 patients,comprising 1191 men and 937 women,were included in our analysis.The regression analyses revealed a negative correlation between the QUICKI score and the 10-year risk of a first hard atherosclerotic car-diovascular event[β=-8.85,CI(-15.77,-1.93)]after adjusting for age,race,body mass index,systolic blood pressure,diastolic blood pressure,hypertension treatment,smoking,diabetes,and low-density lipoprotein cholesterol.Conversely,an increase in HOMA-βwas associated with 10-year risk[β=6.84,CI(0.45,13.23)].Gender-specific subgroup analysis indicated that the QUICKI had aβvalue of 0.077(0.046,0.108)for men and 0.080(0.061,0.094)for women.Conclusion This study demonstrated that increased insulin resistance is linked to an increased risk of cardiovascular disease.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
Objective:To investigate whether nacre extract improves insulin sensitivity,brain glucose metabolism,and cognitive function in diabetic mice.Methods:Diabetic KK-Ay mice(n=5/group)were fed a standard diet or diets supp...Objective:To investigate whether nacre extract improves insulin sensitivity,brain glucose metabolism,and cognitive function in diabetic mice.Methods:Diabetic KK-Ay mice(n=5/group)were fed a standard diet or diets supplemented with nacre extract(125 or 250 mg/kg)for 13 weeks.Metabolic status was assessed by measuring fasting glucose and insulin levels,HOMA-IR,glucose tolerance,and insulin tolerance.The expression of IRS-1,IRS-2,and GLUT4 in the brain was analyzed by qPCR,Western blotting,and immunohistochemistry.Cognitive and anxiety-like behaviors were evaluated using the Y-maze,novel object recognition,Barnes maze,and open field tests.Results:Nacre extract significantly reduced fasting glucose and insulin levels,improved HOMA-IR,and enhanced glucose and insulin tolerance(P<0.05)in diabetic mice.It also restored GLUT4 expression and significantly upregulated SIRT1 and BDNF.Behavioral assessments showed significant improvements in memory and reduced anxiety-like behaviors.Conclusions:Nacre extract enhances insulin sensitivity,improves brain glucose metabolism,and alleviates cognitive and emotional dysfunction in diabetic mice.Further studies are warranted to verify the exact molecular mechanisms and efficacy of nacre extract in diabetes-associated metabolic and neurocognitive dysfunction.展开更多
Objective:To evaluate the antidiabetic effect of Salsola imbricata(S.imbricata)leaf extract against high-fat-diet/streptozocin-induced alterations in diabetic rats and to explore the underlying mechanisms involved in ...Objective:To evaluate the antidiabetic effect of Salsola imbricata(S.imbricata)leaf extract against high-fat-diet/streptozocin-induced alterations in diabetic rats and to explore the underlying mechanisms involved in insulin secretion.Methods:The total phytochemical content of ethyl acetate extract of S.imbricata was analyzed by HPLC.In vitro antioxidant and antidiabetic activities were determined.Ethyl acetate extract of S.imbricata(250 and 500 mg/kg)was administered to diabetic rats for 21 days.Serum glucose,serum insulin,fasting blood glucose,body weight,and homeostasis model assessment of insulin resistance were measured.The hepatic malondialdehyde and antioxidant enzyme activities including superoxide dismutase,catalase,and glutathione peroxidase were evaluated.Sandwich ELISA kits were used to measure pro-inflammatory cytokines IL-6 and tumor necrosis factor-α(TNF-α)in liver tissue homogenate.Pdx-1,Ins-1,and Ins-2 expression levels were assessed using qRT-PCR.Results:S.imbricata had potent antioxidant(IC50=11.75µg/mL)and antidiabetic activity(IC50=28.10µg/mL).HPLC analysis showed the presence of gallic acid,p-coumaric acid,salicylic acid,chlorogenic acid,caffeic acid,and quercetin.S.imbricata extract significantly(P<0.05)reduced blood glucose levels with marked improvement in insulin sensitivity and reduced insulin resistance.S.imbricata leaf extract improved malondialdehyde,superoxide dismutase,catalase,and glutathione peroxidase levels in hepatic tissue.S.imbricata leaf extract also decreased levels of TNF-αand IL-6(P<0.05).qRT-PCR revealed the upregulation of insulin signaling transduction genes(Pdx-1,Ins-1,Ins-2).Conclusions:S.imbricata ethyl acetate extract exhibits pronounced antidiabetic activity in rats by improving insulin resistance via modulation of insulin signaling pathway and alleviating oxidative stress.展开更多
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.
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.
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.
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.
文摘OBJECTIVE To explore hypoglycemic effect of 95%ethanol fraction of Nitraria roborowskii Kom(NRK-C)and its possible mechanism evaluated in the type 2 diabetes mellitus(T2DM)mice.METHODS The body weight,organ indices,blood glucose levels,serum biochemical indexes,as well as HE/PAS histopathological section were all analyzed to assess the hypoglycemic effect of NRK-C in T2DM mice induced by a high-fat diet(HFD)combined with six intraperitoneal injections of 35 mg·kg^(-1)of streptozotocin(STZ).The Western blotting and immunofluorescence were further applied to determine the regulatory effect of NRK-C on key signaling proteins.RESULTS The fasting blood glucose levels were significantly reduced after 7 weeks of administration of NRK-C.In addition,NRK-C could also significantly improve glucose tolerance,hepatic glycogen levels,and lipid levels(total cholesterol,triglyceride,low density lipoprotein and high density lipoprotein),and significantly reduced insulin resistance of diabetic mice,which played an important role in the antidiabetic effects.Further mechanism research demonstrated that phosphorylated PI3K expression was up-regulated and p-GSK3βexpression was up-regulated after NRK-C intervention,indicating that NRK-C might exert a potential antidiabetic effect by modulating the PI3K/AKT signaling pathway.CONCLUSION All these results suggested that NRK-C might improve T2DM and had the potential to be used as an adjunctive therapy.
文摘This editorial discusses the findings of Elbarky et al on the role of selenoprotein P1(SEPP1)in pediatric obesity and insulin resistance.Their study uncovered si-gnificantly lower SEPP1 Levels in children who were obese compared with hea-lthy peers,demonstrating a negative correlation between SEPP1 levels and mea-sures of adiposity and insulin resistance.These findings suggest that SEPP1 is a biomarker useful in the early identification of insulin resistance in pediatric populations.This editorial emphasizes the clinical implications of the study and calls for further research to validate and explore the role of SEPP1 in metabolic health.
文摘Insulin resistance(IR)is widely recognized as a key contributor to metabolic disorders,and various surrogate indices have been developed to estimate IR in clinical and research settings.The hyperinsulinemic-euglycemic clamp is considered the gold standard method for assessing insulin resistance due to its precision;however,its complexity limits its widespread clinical application.Consequently,surrogate indices derived from fasting and post-load glucose and insulin levels have been developed to estimate IR,facilitating early detection and risk stratification in metabolic disorders.This mini-review discusses the clinical utility,strengths,and limitations of key IR indices,including the homeostasis model assessment of IR,quantitative insulin sensitivity check index,Matsuda index,and triglyceride-glucose index.Overall,the evidence presented to date suggests that these indices provide valuable estimates of IR in various popula-tions.Yet,their applicability varies depending on ethnic background,disease status,and clinical setting.Integrating these indices into routine clinical practice and research could improve metabolic risk assessment and guide preventive interventions.Further investigations are necessary to refine their accuracy and determine optimal cut-off values for various populations.
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.
基金Supported by the Key Research and Development Plan of Hunan Province,No.2022SK2013Central South University,No.2024ZZTS0931.
文摘BACKGROUND Cardiovascular disease represents a major complication in patients with type 2 diabetes mellitus(T2DM),with insulin resistance(IR)recognized as a key underlying pathophysiological mechanism.The metabolic score for IR(METS-IR),a simple,non-invasive,and insulin-independent surrogate marker of IR,has been validated for risk stratification and prognostic assessment in conditions such as hypertension,ischemic cardiomyopathy,and T2DM.Monitoring fluctuations in METS-IR levels among individuals with T2DM may facilitate early identification of elevated cardiovascular risk and inform timely therapeutic adjustments.AIM To investigate the association between METS-IR and cardiovascular risk in patients with T2DM and to evaluate its potential utility as a predictive biomarker.METHODS This study represents a secondary analysis of a multicenter randomized controlled trial,ultimately including 10191 patients with T2DM aged 40 years to 79 years,with a follow-up duration of approximately 10 years.Baseline METS-IR was calculated using triglycerides,body mass index,high-density lipoprotein cholesterol and fasting plasma glucose.The predictive value of METS-IR for major adverse cardiovascular events(MACEs),all-cause mortality,congestive heart failure,and major coronary heart disease events,was assessed using Cox proportional hazards models,restricted cubic spline analysis,and stratified subgroup analyses.Multivariable adjustments were performed to account for potential confounding factors.RESULTS The incidence of MACEs increased steadily across higher METS-IR quartiles.After adjusting for multiple confounding factors,hazard ratios comparing the highest to the lowest METS-IR quartile were 1.25[95%confidence interval(CI):1.08-1.45]for MACEs,1.55(95%CI:1.23-1.96)for cardiovascular death,1.39(95%CI:1.21-1.59)for allcause mortality,2.22(95%CI:1.74-2.82)for congestive heart failure,and 1.35(95%CI:1.17-1.56)for major coronary heart disease.Restricted cubic spline analysis supported a positive,dose-dependent relationship between rising METS-IR levels and cardiovascular risk.Moreover,adding METS-IR to conventional risk prediction models enhanced their performance,as evidenced by improvements in the C-statistic,net reclassification improvement,and integrated discrimination improvement.Subgroup analyses indicated possible interactions between METS-IR,hemoglobin A1c levels,and aspirin therapy.CONCLUSION METS-IR shows a strong correlation with cardiovascular risk in individuals with T2DM.Tracking METS-IR levels could enhance risk assessment and the prediction of cardiovascular events.
基金supported by Hostital Capability Enhancement Project of Xiyuan Hospital,CACMS.(No.XYZX0405-25).
文摘Objective This study aimed to investigate the association between insulin resistance and the risk of cardiovascular disease.Methods A cross-sectional study including 2128 participants aged 40-79 years was conducted using data from the National Health and Nutrition Examination Survey from 1999 to 2018.The quantitative insulin sensitivity check index(QUICKI)and homeostasis model assessment ofβ-cell function(HOMA-β)were used as independent variables.The 10-year risk of a first hard atherosclerotic cardiovascular event was used as the dependent variable,with other potential confounding factors considered.Multivariate linear regression models and smooth curve fitting were used to assess the associations between insulin resistance and 10-year risk.Results A total of 2128 patients,comprising 1191 men and 937 women,were included in our analysis.The regression analyses revealed a negative correlation between the QUICKI score and the 10-year risk of a first hard atherosclerotic car-diovascular event[β=-8.85,CI(-15.77,-1.93)]after adjusting for age,race,body mass index,systolic blood pressure,diastolic blood pressure,hypertension treatment,smoking,diabetes,and low-density lipoprotein cholesterol.Conversely,an increase in HOMA-βwas associated with 10-year risk[β=6.84,CI(0.45,13.23)].Gender-specific subgroup analysis indicated that the QUICKI had aβvalue of 0.077(0.046,0.108)for men and 0.080(0.061,0.094)for women.Conclusion This study demonstrated that increased insulin resistance is linked to an increased risk of cardiovascular disease.
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.
文摘Objective:To investigate whether nacre extract improves insulin sensitivity,brain glucose metabolism,and cognitive function in diabetic mice.Methods:Diabetic KK-Ay mice(n=5/group)were fed a standard diet or diets supplemented with nacre extract(125 or 250 mg/kg)for 13 weeks.Metabolic status was assessed by measuring fasting glucose and insulin levels,HOMA-IR,glucose tolerance,and insulin tolerance.The expression of IRS-1,IRS-2,and GLUT4 in the brain was analyzed by qPCR,Western blotting,and immunohistochemistry.Cognitive and anxiety-like behaviors were evaluated using the Y-maze,novel object recognition,Barnes maze,and open field tests.Results:Nacre extract significantly reduced fasting glucose and insulin levels,improved HOMA-IR,and enhanced glucose and insulin tolerance(P<0.05)in diabetic mice.It also restored GLUT4 expression and significantly upregulated SIRT1 and BDNF.Behavioral assessments showed significant improvements in memory and reduced anxiety-like behaviors.Conclusions:Nacre extract enhances insulin sensitivity,improves brain glucose metabolism,and alleviates cognitive and emotional dysfunction in diabetic mice.Further studies are warranted to verify the exact molecular mechanisms and efficacy of nacre extract in diabetes-associated metabolic and neurocognitive dysfunction.
文摘Objective:To evaluate the antidiabetic effect of Salsola imbricata(S.imbricata)leaf extract against high-fat-diet/streptozocin-induced alterations in diabetic rats and to explore the underlying mechanisms involved in insulin secretion.Methods:The total phytochemical content of ethyl acetate extract of S.imbricata was analyzed by HPLC.In vitro antioxidant and antidiabetic activities were determined.Ethyl acetate extract of S.imbricata(250 and 500 mg/kg)was administered to diabetic rats for 21 days.Serum glucose,serum insulin,fasting blood glucose,body weight,and homeostasis model assessment of insulin resistance were measured.The hepatic malondialdehyde and antioxidant enzyme activities including superoxide dismutase,catalase,and glutathione peroxidase were evaluated.Sandwich ELISA kits were used to measure pro-inflammatory cytokines IL-6 and tumor necrosis factor-α(TNF-α)in liver tissue homogenate.Pdx-1,Ins-1,and Ins-2 expression levels were assessed using qRT-PCR.Results:S.imbricata had potent antioxidant(IC50=11.75µg/mL)and antidiabetic activity(IC50=28.10µg/mL).HPLC analysis showed the presence of gallic acid,p-coumaric acid,salicylic acid,chlorogenic acid,caffeic acid,and quercetin.S.imbricata extract significantly(P<0.05)reduced blood glucose levels with marked improvement in insulin sensitivity and reduced insulin resistance.S.imbricata leaf extract improved malondialdehyde,superoxide dismutase,catalase,and glutathione peroxidase levels in hepatic tissue.S.imbricata leaf extract also decreased levels of TNF-αand IL-6(P<0.05).qRT-PCR revealed the upregulation of insulin signaling transduction genes(Pdx-1,Ins-1,Ins-2).Conclusions:S.imbricata ethyl acetate extract exhibits pronounced antidiabetic activity in rats by improving insulin resistance via modulation of insulin signaling pathway and alleviating oxidative stress.
