Insulin is a peptide hormone secreted by pancreaticβ-cells,which plays a key role in regulating glucose metabolism and is the only hormone in the body capable of lowering blood glucose level.The development of insuli...Insulin is a peptide hormone secreted by pancreaticβ-cells,which plays a key role in regulating glucose metabolism and is the only hormone in the body capable of lowering blood glucose level.The development of insulin preparations has undergone nearly 100 years of history,from early animal insulin extraction to modern synthetic insulin and insulin analogs,which have greatly advanced the treatment of diabetes.The insulin receptor has a wide distribution in the body,and its activation leads to intracellular signaling mainly through two pathways,PI3K/Akt and Ras/MAPK.Clinically,insulin is crucial in the treatment and management of diabetes and its complications,especially in the cases where oral medications fail to control blood glucose.The role of insulin is not limited to the regulation of blood glucose but has a wide range of functions throughout the body,such as regulation of mitochondrial function and metabolism,the promotion of protein synthesis,adipogenesis,and cellular proliferation.However,insulin overdose may lead to severe hypoglycemia,which,if left untreated,poses the risk of irreversible neurological damage or even fatality.In this paper,we review the history of the development of insulin preparations,the molecular structure of insulin,the biological processes initiated by insulin and insulin deficiency/resistance.The overview of side effects from insulin is also included in this review.We assume that future research could focus on refining insulin analogs for greater therapeutic precision,minimizing side effects,and extending benefits beyond glycemic control.Exploring insulin’s additional effects may unlock potential applications in treating multiple diseases.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
BACKGROUND There is a lack of clinical evidence on the efficacy and safety of transitioning from a thrice-daily pre-mixed insulin or basal-prandial regimen to insulin degludec/aspart(IDegAsp)therapy,with insufficient ...BACKGROUND There is a lack of clinical evidence on the efficacy and safety of transitioning from a thrice-daily pre-mixed insulin or basal-prandial regimen to insulin degludec/aspart(IDegAsp)therapy,with insufficient data from the Chinese population.AIM To demonstrate the efficacy,safety,and treatment satisfaction associated with the transition to IDegAsp in type 2 diabetes mellitus(T2DM).METHODS In this 12-week open-label,non-randomized,single-center,pilot study,patients with T2DM receiving thrice-daily insulin or intensive insulin treatment were transitioned to twice-daily injections of insulin IDegAsp.Insulin doses,hemoglobin A1c(HbA1c)levels,fasting blood glucose(FBG),hypoglycemic events,a Diabetes Treatment Satisfaction Questionnaire,and other parameters were assessed at baseline and 12-weeks.RESULTS This study included 21 participants.A marked enhancement was observed in the FBG level(P=0.02),daily total insulin dose(P=0.03),and overall diabetes treatment satisfaction(P<0.01)in the participants who switched to IDegAsp.There was a decrease in HbA1c levels(7.6±1.1 vs 7.4±0.9,P=0.31)and the frequency of hypoglycemic events of those who switched to IDegAsp decreased,however,there was no statistically significant difference.CONCLUSION The present findings suggest that treatment with IDegAsp enhances clinical outcomes,particularly FBG levels,daily cumulative insulin dose,and overall satisfaction with diabetes treatment.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
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
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
Premixed insulin combines two types of insulin in a single injection.This combination streamlines dosing for patients with type 1 or type 2 diabetes,thereby enhancing convenience.However,patients receiving premixed in...Premixed insulin combines two types of insulin in a single injection.This combination streamlines dosing for patients with type 1 or type 2 diabetes,thereby enhancing convenience.However,patients receiving premixed insulin commonly have less satisfactory blood glucose control.The fixed ratio of insulin in these formulations frequently fails to account for the nuanced demands of individualized glucose-lowering therapy.Moreover,local absorption of mixed insulin and potential systemic autoimmune responses may further compromise glycaemic control.The co-formulation of insulin degludec and insulin aspart introduces a new combination of the two insulin types within a single injection,offering a promising solution for mitigating the limitations inherent in premixed insulin.展开更多
1.Exercise enhances muscle function and insulin sensitivity Skeletal muscle plays a fundamental role in not only locomotion,but also systemic metabolism.In people with type 2 diabetes,skeletal muscle is a major site o...1.Exercise enhances muscle function and insulin sensitivity Skeletal muscle plays a fundamental role in not only locomotion,but also systemic metabolism.In people with type 2 diabetes,skeletal muscle is a major site of insulin resistance,with impaired insulin signaling and reduced glucose transport activity contributing to metabolic dysfunction.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
BACKGROUND Studies have shown that patients with type 1 diabetes mellitus on continuous subcutaneous insulin infusion(CSII)require a lower dose of insulin than those treated with multiple daily injections(MDIs).Howeve...BACKGROUND Studies have shown that patients with type 1 diabetes mellitus on continuous subcutaneous insulin infusion(CSII)require a lower dose of insulin than those treated with multiple daily injections(MDIs).However,it is unclear whether this is also the case for patients with type 2 diabetes mellitus(T2DM).AIM To compare insulin dosage requirements between CSII and MDI in T2DM,iden-tifying influencing factors associated with both therapeutic modalities.METHODS A total of 954 patients with T2DM were divided into two groups:CSII and MDI groups.The total daily insulin dose(TDD),TDD per kilogram per day(TDD/kg),and ratio of total basal insulin dose to TDD(%TBa)required to achieve the target blood glucose levels were compared between the two groups.In addition,factors affecting insulin dosage were analyzed in both groups of patients.RESULTS Compared to the CSII group,the MDI group required a higher TDD[median(interquartile)]:30.00(24.00,38.00)U/day vs 26.40(21.60,32.40)U/day;P<0.01,TDD/kg and%TBa.In the MDI group and CSII groups,an increase in TDD was independently associated with an increase in body mass index(BMI),waist circumference(WC),fasting plasma glucose(FPG),and glycated hemoglobin(HbA1c).The pathophysiology of type 2 diabetes mellitus(T2DM)mainly involves insulin resistance and progressiveβ-cell failure,which leads to increased blood glucose levels(hyperglycemia)[1-3].Treatment for T2DM includes antidiabetic medications and insulin therapy[4,5].Patients with T2DM withβ-cell failure usually require insulin therapy[6-8].Continuous subcutaneous insulin infusion(CSII)and multiple daily injections(MDIs)are two major insulin therapies for controlling hyperglycemia in these patients.However,excessive insulin therapies may cause problems such as hypoglycemia,weight gain,and iatrogenic hyperinsulinemia[9].Therefore,attention should be paid to the dosage of insulin used.The establishment of insulin regimens for CSII and MDI therapies is primarily guided by physicians’empirical judgment.To date,there have been few clear guidelines or recommendations on the appropriate insulin dose during CSII and MDI treatment for T2DM[10].Yang et al[11]studied insulin doses and related factors in the CSII treatment of patients with T2DM[12].However,these studies did not cover the dose setting and related factors in MDI treatment.Previous studies have shown that patients with type 1 diabetes mellitus treated with CSII require less insulin than those treated with MDIs[13-15].However,it is unclear whether patients with T2DM on CSII also require less insulin than patients on MDI.Therefore,the present study determined the difference in insulin dosages between CSII and MDI therapies and evaluated the related factors in patients with T2DM.It also systematically analyzed the insulin dose characteristics of MDI and CSII in 954 hospitalized patients with T2DM,aiming to optimize the insulin dosage regimen and provide clinical references for guiding the application of CSII and MDI in patients with T2DM.展开更多
BACKGROUND Type 2 diabetes mellitus(T2DM)often leads to vascular complications,such as albuminuria.The role of insulin autoantibodies(IAA)and their interaction with D-dimer in this context remains unclear.AIM To inves...BACKGROUND Type 2 diabetes mellitus(T2DM)often leads to vascular complications,such as albuminuria.The role of insulin autoantibodies(IAA)and their interaction with D-dimer in this context remains unclear.AIM To investigate the characteristics of IAA and its effect on albuminuria in T2DM patients.METHODS We retrospectively analyzed clinical data from 115 T2DM patients with positive IAA induced by exogenous insulin,and 115 age-and sex-matched IAA-negative T2DM patients as controls.Propensity scores were calculated using multivariate logistic regression.Key variables were selected using the least absolute shrinkage and selection operator(LASSO)algorithm.We constructed a prediction model and analyzed the association between IAA and albuminuria based on demographic and laboratory parameters.RESULTS The IAA-positive group had significantly higher D-dimer levels[0.30(0.19-0.55)mg/L vs 0.21(0.19-0.33)mg/L,P=0.008]and plasma insulin levels[39.1(12.0-102.7)μU/mL vs 9.8(5.5-17.6)μU/mL,P<0.001]compared to the IAA-negative group.Increases in the insulin dose per weight ratio,diabetes duration,and urinary albumin-to-creatinine ratio(UACR)were observed but did not reach statistical significance.The LASSO model identified plasma insulin and D-dimer as key factors with larger coefficients.D-dimer was significantly associated with UACR in the total and IAA-positive groups but not in the IAA-negative group.The odds ratio for D-dimer elevation(>0.5 g/L)was 2.88(95%confidence interval:1.17-7.07)in the IAA-positive group(P interaction<0.05).CONCLUSION D-dimer elevation is an independent risk factor for abnormal albuminuria and interacts with IAA in the development of abnormal albuminuria in T2DM patients.展开更多
Parkinson's disease(PD),a chronic and com-mon neurodegenerative disease,is characterized by the progressive loss of dopaminergic neurons in the dense part of the substantia nigra and abnormal aggregation of alpha-...Parkinson's disease(PD),a chronic and com-mon neurodegenerative disease,is characterized by the progressive loss of dopaminergic neurons in the dense part of the substantia nigra and abnormal aggregation of alpha-synuclein.Type 2 diabetes mellitus(T2DM)is a metabolic disease characterized by chronic insulin resistance and deficiency in insulin secretion.Extensive evidence has con-firmed shared pathogenic mechanisms underlying PD and T2DM,such as oxidative stress caused by insulin resistance,mitochondrial dysfunction,inflammation,and disorders of energy metabolism.Conventional drugs for treating T2DM,such as metformin and glucagon-like peptide-1 receptor ago-nists,affect nerve repair.Even drugs for treating PD,such as levodopa,can affect insulin secretion.This review sum-marizes the relationship between PD and T2DM and related therapeutic drugs from the perspective of insulin signaling pathways in the brain.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
BACKGROUND Thyrotoxic periodic paralysis(TPP)is an endocrine emergency caused by thyrotoxicosis,manifesting mainly as periodic myasthenia and hypokalemia,and posing a serious threat to the patient's health.Fatigue...BACKGROUND Thyrotoxic periodic paralysis(TPP)is an endocrine emergency caused by thyrotoxicosis,manifesting mainly as periodic myasthenia and hypokalemia,and posing a serious threat to the patient's health.Fatigue,strenuous exercise,alcohol abuse,high carbohydrate intake and insulin injections are common triggers of paralysis.This article reports a case of severe TPP induced by insulin injection,elucidates the characteristics and pathogenesis of the disease,analyses the risk factors for triggering TPP,and hopefully provides more clinical data for TPP patients.CASE SUMMARY A 38-year-old Asian man presented to the emergency department with a oneweek history of limb weakness and worsening half-day.His medical history included poorly controlled type 2 diabetes and he had been switched to Aspart50 a week earlier.He was alert and oriented with upper extremity strength grade 3 and lower extremity strength grade 1.Emergency department tests showed hypokalemia of 1.6 mmol/L.The paramedics administered 1.5 g of potassium intravenously,followed by 4.0 g orally.Weakness in the arms and legs improved.He was referred to endocrinology where he was diagnosed with Graves'disease,with suboptimal control and insulin injections possibly causing TPP.We stopped his insulin and he was discharged with a potassium level of 4.0 mmol/L.CONCLUSION Insulin is a trigger for TPP and should be avoided in patients with hyperthyroidism.Early recognition and treatment of TPP is crucial,especially in patients presenting with hypokalemic periodic paralysis.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
Background: Diabetes mellitus (DM) is a disease characterized by hyperglycemia due to (a) insulin-insufficiency (type I DM), or (b) impaired glucose cell-entry (insulin resistance) due to the downregulation of insulin...Background: Diabetes mellitus (DM) is a disease characterized by hyperglycemia due to (a) insulin-insufficiency (type I DM), or (b) impaired glucose cell-entry (insulin resistance) due to the downregulation of insulin cell receptors (type II DM). Type I DM usually presents with florid manifestations contrary to a slowly-progressive type II. Patients and methods: Over the past 10 years, we encountered 9 obese patients with controlled insulin-requiring type II DM for years, at a dose of 62 ± 5 units/day, who developed sudden and severe insulin resistance (IR) that required 210 ± 25 units daily. All patients had very high levels of anti-Glutamic Acid Decarboxylase (GAD) antibodies. Despite a lack of previous testing for anti-GAD antibodies, they were treated, with Cyclosporin A (Cy), as an autoimmune disorder superimposed on their type II MD. Initially all patients were treated with 100 mg, of Cy, twice daily aiming at an initial trough level of 100 - 150 ng/ml. Three months later, the dose was reduced to 50 mg twice daily for a total of 2 years. Results: Amelioration of IR was achieved by 1 month with a reduction of daily insulin requirement to 123 ± 16 units that further decreased to 76 ± 11 by the end of the 3rd month. Such improvement persisted for 2 years and >1 year after Cy discontinuation. Moreover, a decline in insulin requirements was associated with a parallel decrease in anti-GAD antibody levels and an increase in C-peptide insulin without kidney disease. Conclusion: Anti-GAD antibodies can induce acute IR in type II DM, and this phenomenon can be treated safely and effectively with Cy.展开更多
Athletes often use branched-chain amino acid (BCAAs) supplements with a ratio of 2:1:1 (leucine:isoleucine:valine) for their impact on muscle building. Research suggests that by altering the ratio, an improvement in g...Athletes often use branched-chain amino acid (BCAAs) supplements with a ratio of 2:1:1 (leucine:isoleucine:valine) for their impact on muscle building. Research suggests that by altering the ratio, an improvement in glucose metabolism might be possible. The purpose of this study was to examine how isoleucine would influence glucose tolerance. We recruited healthy male (n = 13) and female (n = 5) participants who were asked to fast for 12 hours before coming to the laboratory. A fasting blood sample was collected, followed by the subjects consuming a breakfast containing 113 g carbohydrates, 8 g protein, 1.5 g fat, and BCAA powder in the 2:1:1 ratio (Control) or BCAA powder enriched with Isoleucine (2:6:1), both added to orange juice. The opposite meal was consumed on a second visit one week apart. Blood was collected at 30, 60, 90, and 120 minutes post-meal. No differences were observed between the Control and Isoleucine for changes in serum glucose or insulin response when examining all subjects together. However, when comparing between genders, males tended to have a significantly lower serum glucose response compared to females when consuming the Isoleucine, with no difference between the genders when consuming the Control. Also, males had significantly lower serum glucose responses when consuming the Isoleucine compared to when they consumed the Control, while females had significantly higher serum glucose responses when consuming the Isoleucine compared to when they consumed the Control. In general, males tended to have a lower serum insulin response than females when consuming both the Control and the Isoleucine. Our study indicates a significant difference in the way genders respond to BCAA supplementation, where isoleucine may improve glucose tolerance and insulin response in males but not females.展开更多
This article reviews recent research progress on the mechanisms by which obesity induces insulin resistance through factors such as endoplasmic reticulum stress,mitochondrial dysfunction,and adipocytokines.The aim is ...This article reviews recent research progress on the mechanisms by which obesity induces insulin resistance through factors such as endoplasmic reticulum stress,mitochondrial dysfunction,and adipocytokines.The aim is to provide more basis for the treatment of this disease.展开更多
Insulin is an essential and versatile protein taking part in the control of blood glucose levels and protein anabolism.However,under prolonged storage or high temperature stress,insulin tends to unfold and aggregate i...Insulin is an essential and versatile protein taking part in the control of blood glucose levels and protein anabolism.However,under prolonged storage or high temperature stress,insulin tends to unfold and aggregate into toxic amyloid fibrils,leading to loss of physiological function.Inspired by natural chaperones,a series of temperature-sensitive polycaprolactone-based micelles were designed to prevent insulin from deactivation.The micelles were fabricated through the self-assembly of amphiphilic copolymers of methoxy poly(ethylene glycol)-poly(4-diethylformamide caprolactone-co-caprolactone)(mPEG_(17)-P(DECL-co-CL)),which had a regular spherical morphology with particle sizes of about 100 nm.In addition,the lower critical solution temperature(LCST)of the micelles could be tuned to 9 and 29℃by changing the ratio of DECL to CL.Benefiting from the temperature-sensitivity of DECL segment,the binding ability of micelles to insulin could be modulated by changing the temperature.Above LCST,micelles effectively inhibited insulin aggregation and protected it from thermal inactivation due to the strong binding ability between the hydrophobic segment DECL and insulin.Below LCST,DECL segment returned to hydrophilic and bound weakly with insulin,leading to the release of insulin and assisting in its recovery of secondary structure.Thus,these temperature-sensitive micelles provided an effective strategy for insulin protection.展开更多
基金supported by grants from National Natural Science Foundation of China(Grant No.82301577).
文摘Insulin is a peptide hormone secreted by pancreaticβ-cells,which plays a key role in regulating glucose metabolism and is the only hormone in the body capable of lowering blood glucose level.The development of insulin preparations has undergone nearly 100 years of history,from early animal insulin extraction to modern synthetic insulin and insulin analogs,which have greatly advanced the treatment of diabetes.The insulin receptor has a wide distribution in the body,and its activation leads to intracellular signaling mainly through two pathways,PI3K/Akt and Ras/MAPK.Clinically,insulin is crucial in the treatment and management of diabetes and its complications,especially in the cases where oral medications fail to control blood glucose.The role of insulin is not limited to the regulation of blood glucose but has a wide range of functions throughout the body,such as regulation of mitochondrial function and metabolism,the promotion of protein synthesis,adipogenesis,and cellular proliferation.However,insulin overdose may lead to severe hypoglycemia,which,if left untreated,poses the risk of irreversible neurological damage or even fatality.In this paper,we review the history of the development of insulin preparations,the molecular structure of insulin,the biological processes initiated by insulin and insulin deficiency/resistance.The overview of side effects from insulin is also included in this review.We assume that future research could focus on refining insulin analogs for greater therapeutic precision,minimizing side effects,and extending benefits beyond glycemic control.Exploring insulin’s additional effects may unlock potential applications in treating multiple diseases.
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.
基金Supported by CAMS Innovation Fund for Medical Sciences,No.2023-I2M-C&T-B-043National High Level Hospital Clinical Research Funding,No.2022-PUMCH-B-015+1 种基金CAMS Innovation Fund for Medical Sciences,No.2021-1-12M-002Beijing Municipal Natural Science Foundation,No.M22014.
文摘BACKGROUND There is a lack of clinical evidence on the efficacy and safety of transitioning from a thrice-daily pre-mixed insulin or basal-prandial regimen to insulin degludec/aspart(IDegAsp)therapy,with insufficient data from the Chinese population.AIM To demonstrate the efficacy,safety,and treatment satisfaction associated with the transition to IDegAsp in type 2 diabetes mellitus(T2DM).METHODS In this 12-week open-label,non-randomized,single-center,pilot study,patients with T2DM receiving thrice-daily insulin or intensive insulin treatment were transitioned to twice-daily injections of insulin IDegAsp.Insulin doses,hemoglobin A1c(HbA1c)levels,fasting blood glucose(FBG),hypoglycemic events,a Diabetes Treatment Satisfaction Questionnaire,and other parameters were assessed at baseline and 12-weeks.RESULTS This study included 21 participants.A marked enhancement was observed in the FBG level(P=0.02),daily total insulin dose(P=0.03),and overall diabetes treatment satisfaction(P<0.01)in the participants who switched to IDegAsp.There was a decrease in HbA1c levels(7.6±1.1 vs 7.4±0.9,P=0.31)and the frequency of hypoglycemic events of those who switched to IDegAsp decreased,however,there was no statistically significant difference.CONCLUSION The present findings suggest that treatment with IDegAsp enhances clinical outcomes,particularly FBG levels,daily cumulative insulin dose,and overall satisfaction with diabetes treatment.
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.
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Premixed insulin combines two types of insulin in a single injection.This combination streamlines dosing for patients with type 1 or type 2 diabetes,thereby enhancing convenience.However,patients receiving premixed insulin commonly have less satisfactory blood glucose control.The fixed ratio of insulin in these formulations frequently fails to account for the nuanced demands of individualized glucose-lowering therapy.Moreover,local absorption of mixed insulin and potential systemic autoimmune responses may further compromise glycaemic control.The co-formulation of insulin degludec and insulin aspart introduces a new combination of the two insulin types within a single injection,offering a promising solution for mitigating the limitations inherent in premixed insulin.
基金supported by the Swedish Research Council(201500165)a Wallenberg Scholars Award from the Knut and Alice Wallenberg Foundation(KAW 2023.0312)The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent research center at the University of Copenhagen,partially funded by an unrestricted donation from the Novo Nordisk Foundation(NNF23SA0084103).
文摘1.Exercise enhances muscle function and insulin sensitivity Skeletal muscle plays a fundamental role in not only locomotion,but also systemic metabolism.In people with type 2 diabetes,skeletal muscle is a major site of insulin resistance,with impaired insulin signaling and reduced glucose transport activity contributing to metabolic dysfunction.
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 the National Key R and D Program of China,No.2021YFC2501700 and No.2021YFC2501705and the National Natural Science Foundation of China,No.82171580 and No.81672646.
文摘BACKGROUND Studies have shown that patients with type 1 diabetes mellitus on continuous subcutaneous insulin infusion(CSII)require a lower dose of insulin than those treated with multiple daily injections(MDIs).However,it is unclear whether this is also the case for patients with type 2 diabetes mellitus(T2DM).AIM To compare insulin dosage requirements between CSII and MDI in T2DM,iden-tifying influencing factors associated with both therapeutic modalities.METHODS A total of 954 patients with T2DM were divided into two groups:CSII and MDI groups.The total daily insulin dose(TDD),TDD per kilogram per day(TDD/kg),and ratio of total basal insulin dose to TDD(%TBa)required to achieve the target blood glucose levels were compared between the two groups.In addition,factors affecting insulin dosage were analyzed in both groups of patients.RESULTS Compared to the CSII group,the MDI group required a higher TDD[median(interquartile)]:30.00(24.00,38.00)U/day vs 26.40(21.60,32.40)U/day;P<0.01,TDD/kg and%TBa.In the MDI group and CSII groups,an increase in TDD was independently associated with an increase in body mass index(BMI),waist circumference(WC),fasting plasma glucose(FPG),and glycated hemoglobin(HbA1c).The pathophysiology of type 2 diabetes mellitus(T2DM)mainly involves insulin resistance and progressiveβ-cell failure,which leads to increased blood glucose levels(hyperglycemia)[1-3].Treatment for T2DM includes antidiabetic medications and insulin therapy[4,5].Patients with T2DM withβ-cell failure usually require insulin therapy[6-8].Continuous subcutaneous insulin infusion(CSII)and multiple daily injections(MDIs)are two major insulin therapies for controlling hyperglycemia in these patients.However,excessive insulin therapies may cause problems such as hypoglycemia,weight gain,and iatrogenic hyperinsulinemia[9].Therefore,attention should be paid to the dosage of insulin used.The establishment of insulin regimens for CSII and MDI therapies is primarily guided by physicians’empirical judgment.To date,there have been few clear guidelines or recommendations on the appropriate insulin dose during CSII and MDI treatment for T2DM[10].Yang et al[11]studied insulin doses and related factors in the CSII treatment of patients with T2DM[12].However,these studies did not cover the dose setting and related factors in MDI treatment.Previous studies have shown that patients with type 1 diabetes mellitus treated with CSII require less insulin than those treated with MDIs[13-15].However,it is unclear whether patients with T2DM on CSII also require less insulin than patients on MDI.Therefore,the present study determined the difference in insulin dosages between CSII and MDI therapies and evaluated the related factors in patients with T2DM.It also systematically analyzed the insulin dose characteristics of MDI and CSII in 954 hospitalized patients with T2DM,aiming to optimize the insulin dosage regimen and provide clinical references for guiding the application of CSII and MDI in patients with T2DM.
文摘BACKGROUND Type 2 diabetes mellitus(T2DM)often leads to vascular complications,such as albuminuria.The role of insulin autoantibodies(IAA)and their interaction with D-dimer in this context remains unclear.AIM To investigate the characteristics of IAA and its effect on albuminuria in T2DM patients.METHODS We retrospectively analyzed clinical data from 115 T2DM patients with positive IAA induced by exogenous insulin,and 115 age-and sex-matched IAA-negative T2DM patients as controls.Propensity scores were calculated using multivariate logistic regression.Key variables were selected using the least absolute shrinkage and selection operator(LASSO)algorithm.We constructed a prediction model and analyzed the association between IAA and albuminuria based on demographic and laboratory parameters.RESULTS The IAA-positive group had significantly higher D-dimer levels[0.30(0.19-0.55)mg/L vs 0.21(0.19-0.33)mg/L,P=0.008]and plasma insulin levels[39.1(12.0-102.7)μU/mL vs 9.8(5.5-17.6)μU/mL,P<0.001]compared to the IAA-negative group.Increases in the insulin dose per weight ratio,diabetes duration,and urinary albumin-to-creatinine ratio(UACR)were observed but did not reach statistical significance.The LASSO model identified plasma insulin and D-dimer as key factors with larger coefficients.D-dimer was significantly associated with UACR in the total and IAA-positive groups but not in the IAA-negative group.The odds ratio for D-dimer elevation(>0.5 g/L)was 2.88(95%confidence interval:1.17-7.07)in the IAA-positive group(P interaction<0.05).CONCLUSION D-dimer elevation is an independent risk factor for abnormal albuminuria and interacts with IAA in the development of abnormal albuminuria in T2DM patients.
基金supported by the National Natural Science Foundation of China(32161143021)the Iran National Science Foundation(4001873)+1 种基金the Henan Province Natural Science Foundation of China(182300410313)Henan University graduate Talent Program of Henan Province(SYLYC2023092).
文摘Parkinson's disease(PD),a chronic and com-mon neurodegenerative disease,is characterized by the progressive loss of dopaminergic neurons in the dense part of the substantia nigra and abnormal aggregation of alpha-synuclein.Type 2 diabetes mellitus(T2DM)is a metabolic disease characterized by chronic insulin resistance and deficiency in insulin secretion.Extensive evidence has con-firmed shared pathogenic mechanisms underlying PD and T2DM,such as oxidative stress caused by insulin resistance,mitochondrial dysfunction,inflammation,and disorders of energy metabolism.Conventional drugs for treating T2DM,such as metformin and glucagon-like peptide-1 receptor ago-nists,affect nerve repair.Even drugs for treating PD,such as levodopa,can affect insulin secretion.This review sum-marizes the relationship between PD and T2DM and related therapeutic drugs from the perspective of insulin signaling pathways in the brain.
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.
文摘BACKGROUND Thyrotoxic periodic paralysis(TPP)is an endocrine emergency caused by thyrotoxicosis,manifesting mainly as periodic myasthenia and hypokalemia,and posing a serious threat to the patient's health.Fatigue,strenuous exercise,alcohol abuse,high carbohydrate intake and insulin injections are common triggers of paralysis.This article reports a case of severe TPP induced by insulin injection,elucidates the characteristics and pathogenesis of the disease,analyses the risk factors for triggering TPP,and hopefully provides more clinical data for TPP patients.CASE SUMMARY A 38-year-old Asian man presented to the emergency department with a oneweek history of limb weakness and worsening half-day.His medical history included poorly controlled type 2 diabetes and he had been switched to Aspart50 a week earlier.He was alert and oriented with upper extremity strength grade 3 and lower extremity strength grade 1.Emergency department tests showed hypokalemia of 1.6 mmol/L.The paramedics administered 1.5 g of potassium intravenously,followed by 4.0 g orally.Weakness in the arms and legs improved.He was referred to endocrinology where he was diagnosed with Graves'disease,with suboptimal control and insulin injections possibly causing TPP.We stopped his insulin and he was discharged with a potassium level of 4.0 mmol/L.CONCLUSION Insulin is a trigger for TPP and should be avoided in patients with hyperthyroidism.Early recognition and treatment of TPP is crucial,especially in patients presenting with hypokalemic periodic paralysis.
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Background: Diabetes mellitus (DM) is a disease characterized by hyperglycemia due to (a) insulin-insufficiency (type I DM), or (b) impaired glucose cell-entry (insulin resistance) due to the downregulation of insulin cell receptors (type II DM). Type I DM usually presents with florid manifestations contrary to a slowly-progressive type II. Patients and methods: Over the past 10 years, we encountered 9 obese patients with controlled insulin-requiring type II DM for years, at a dose of 62 ± 5 units/day, who developed sudden and severe insulin resistance (IR) that required 210 ± 25 units daily. All patients had very high levels of anti-Glutamic Acid Decarboxylase (GAD) antibodies. Despite a lack of previous testing for anti-GAD antibodies, they were treated, with Cyclosporin A (Cy), as an autoimmune disorder superimposed on their type II MD. Initially all patients were treated with 100 mg, of Cy, twice daily aiming at an initial trough level of 100 - 150 ng/ml. Three months later, the dose was reduced to 50 mg twice daily for a total of 2 years. Results: Amelioration of IR was achieved by 1 month with a reduction of daily insulin requirement to 123 ± 16 units that further decreased to 76 ± 11 by the end of the 3rd month. Such improvement persisted for 2 years and >1 year after Cy discontinuation. Moreover, a decline in insulin requirements was associated with a parallel decrease in anti-GAD antibody levels and an increase in C-peptide insulin without kidney disease. Conclusion: Anti-GAD antibodies can induce acute IR in type II DM, and this phenomenon can be treated safely and effectively with Cy.
文摘Athletes often use branched-chain amino acid (BCAAs) supplements with a ratio of 2:1:1 (leucine:isoleucine:valine) for their impact on muscle building. Research suggests that by altering the ratio, an improvement in glucose metabolism might be possible. The purpose of this study was to examine how isoleucine would influence glucose tolerance. We recruited healthy male (n = 13) and female (n = 5) participants who were asked to fast for 12 hours before coming to the laboratory. A fasting blood sample was collected, followed by the subjects consuming a breakfast containing 113 g carbohydrates, 8 g protein, 1.5 g fat, and BCAA powder in the 2:1:1 ratio (Control) or BCAA powder enriched with Isoleucine (2:6:1), both added to orange juice. The opposite meal was consumed on a second visit one week apart. Blood was collected at 30, 60, 90, and 120 minutes post-meal. No differences were observed between the Control and Isoleucine for changes in serum glucose or insulin response when examining all subjects together. However, when comparing between genders, males tended to have a significantly lower serum glucose response compared to females when consuming the Isoleucine, with no difference between the genders when consuming the Control. Also, males had significantly lower serum glucose responses when consuming the Isoleucine compared to when they consumed the Control, while females had significantly higher serum glucose responses when consuming the Isoleucine compared to when they consumed the Control. In general, males tended to have a lower serum insulin response than females when consuming both the Control and the Isoleucine. Our study indicates a significant difference in the way genders respond to BCAA supplementation, where isoleucine may improve glucose tolerance and insulin response in males but not females.
基金Supported by National Natural Science Foundation of China(82174525)Natural Science Foundation of Jilin Province(YDZJ202301ZYTS469)+1 种基金Science and Technology Research Project of the Department of Education of Jilin Province(JJKH20230966KJ)Jilin Province College Students'Innovation and Entrepreneurship Training Program(S202310199043,S202310199042,S202510199020).
文摘This article reviews recent research progress on the mechanisms by which obesity induces insulin resistance through factors such as endoplasmic reticulum stress,mitochondrial dysfunction,and adipocytokines.The aim is to provide more basis for the treatment of this disease.
基金financially supported by the National Natural Science Foundation of China(Nos.52273009 and 21674037).
文摘Insulin is an essential and versatile protein taking part in the control of blood glucose levels and protein anabolism.However,under prolonged storage or high temperature stress,insulin tends to unfold and aggregate into toxic amyloid fibrils,leading to loss of physiological function.Inspired by natural chaperones,a series of temperature-sensitive polycaprolactone-based micelles were designed to prevent insulin from deactivation.The micelles were fabricated through the self-assembly of amphiphilic copolymers of methoxy poly(ethylene glycol)-poly(4-diethylformamide caprolactone-co-caprolactone)(mPEG_(17)-P(DECL-co-CL)),which had a regular spherical morphology with particle sizes of about 100 nm.In addition,the lower critical solution temperature(LCST)of the micelles could be tuned to 9 and 29℃by changing the ratio of DECL to CL.Benefiting from the temperature-sensitivity of DECL segment,the binding ability of micelles to insulin could be modulated by changing the temperature.Above LCST,micelles effectively inhibited insulin aggregation and protected it from thermal inactivation due to the strong binding ability between the hydrophobic segment DECL and insulin.Below LCST,DECL segment returned to hydrophilic and bound weakly with insulin,leading to the release of insulin and assisting in its recovery of secondary structure.Thus,these temperature-sensitive micelles provided an effective strategy for insulin protection.
