Objective decline of resistance whether H Type 2 diabetes has been recently recognized as an important risk factor for cognitive patients with Alzheimer＇s disease （AD）. But the roles of hyperinsulinemia （HI） and...Objective decline of resistance whether H Type 2 diabetes has been recently recognized as an important risk factor for cognitive patients with Alzheimer＇s disease （AD）. But the roles of hyperinsulinemia （HI） and insulin （IR） in the development of AD are still controversial. This study was designed to evaluate or IR influenced the cognitive functions of older cohort. Methods The cognitive functions of 328 consecutive elderly patients were evaluated with a battery of cognitive rating scales. Their fasting blood glucose （FBG） and fasting insulin （FINS） were analyzed and IR was calculated with modified-Homa. The cognitive scores in different groups and the correlation of cognitive functions with HI or IR were analyzed. Results In our study, there were 180 participants with HI and 148 without HI, and 192 with iR and 136 without IR. The participants with HI showed worse cognitive functions than those without HI in MMSE, MOCA, CDR, orientation, delayed memory, and attention/calculation domains. Similarly, the elderly with IR had lower cognitive scores than those without IR in MMSE, MOCA, CDR, GDS, orientation, delayed memory, and attention/calculation domains. The insulin levels and Homa IR had negative correlation with the scores of MMSE and delayed memory, not only in the model I adjusted for FBG and diabetes history, but also in the model 2 adjusted for all nine demographic characteristics. Conclusion HI and IR are important risk factors for cognitive decline of the elderly, especially for the dysfunctions in delayed memory domains.展开更多
Nutritional supplementation has long been studied as a possible treatment alternative or as an adjunct to the standard treatments for common ailments and diseases.According to the latest research,the Chilean maqui ber...Nutritional supplementation has long been studied as a possible treatment alternative or as an adjunct to the standard treatments for common ailments and diseases.According to the latest research,the Chilean maqui berry,Aristotelia chilensis,has been shown to reduce postprandial insulin levels by as much as fifty percent.The berry,which has been shown to be as effective as metformin at increasing insulin sensitivity and controlling blood glucose levels,follows a simple mechanism of action that involves the inhibition of sodium dependent glucose transporters in the small intestine,slowing the rate at which sugars enter the bloodstream and thereby decreasing blood sugar spikes and the corresponding increase in insulin levels.Chronically high blood glucose levels have been proven to play a significant role in the development of cancers,as diabetics and prediabetics have been proven to have elevated risk of developing cancerous growth.Consistent dietary supplementation with maqui berry may therefore indirectly reduce the risk of cancer,as well as other diseases which respond negatively to hyperglycemia and hyperinsulinemia.展开更多
Inflammation induces insulin resistance and hyperinsulinemia due to elevation of serum cytokines such as tumor necrosis factor-α and interleukins. Chronic myeloproliferative diseases including myelofibrosis show high...Inflammation induces insulin resistance and hyperinsulinemia due to elevation of serum cytokines such as tumor necrosis factor-α and interleukins. Chronic myeloproliferative diseases including myelofibrosis show higher serum interleukin levels than healthy subjects, which has been suggested to be the useful markers for disease activity. However, an association between myelofibrosis and insulin resistance has not ever been discussed anywhere. Here we report a case of type 2 diabetes showing remarkable hyperinsulinemia and insulin resistance possibly due to myelofibrosis.展开更多
Backgrounds: Differences in serum lipids profiles in different type of glucose intolerance are unclear. Aims: To characterize lipid profiles in different type of glucose intolerance, and to assess relationships betwee...Backgrounds: Differences in serum lipids profiles in different type of glucose intolerance are unclear. Aims: To characterize lipid profiles in different type of glucose intolerance, and to assess relationships between serum lipids profile and disturbance of glucose metabolism in prediabetic subjects. Methods: Using the measurements in medical check-up with 75 goral glucose tolerance test (OGTT), total of 620 male subjects, who are not on medications for metabolic diseases or hypertension, were divided into normal fasting glucose and glucose tolerance (NFG/ NGT), isolated impaired fasting glucose (iIFG), isolated impaired glucose tolerance (iIGT) and combined IFG and IGT (IFG/IGT) based on results of the OGTT. Results: Age and body mass index (BMI) were similar in the four groups. Matsuda index (an index of whole body insulin sensitivity) was lower in iIFG, iIGT and IFG/IGT as compared with NFG/NGT. Plasma insulin excursion during the OGTT was significantly higher in IFG/IGT versus NFG/NGT. Serum triglyceride level (TG) and TG to HDL ratio (TG/HDL) were higher in IFG/IGT versus NFG/NGT. Matsuda index was positively correlated with HDL and was inversely correlated with TG, LDL, non-HDL, TG/ HDL and LDL to HDL ratio (LDL/HDL). Backward stepwise multiple regression analysis indicated that increases in BMI, plasma insulin level at 60 min (PI60) and plasma glucose level at 120 min in the OGTT were independently associated with increases in TG and TG/HDL. Increases in BMI and PI60 were related to an increase in non-HDL and LDL/HDL and a decrease in HDL. Conclusions: These results indicate that postprandial hyperglycemia and hyperinsulinemia based on advanced insulin resistance are closely related to lipid risk factors of atherosclerotic macrovascular disease in prediabetic subjects.展开更多
AIM:To examine skin perfusion in dependency on insulinemia in healthy subjects.METHODS:All volunteers were informed in detail about the procedures and signed informed consent.The protocol of this study was approved by...AIM:To examine skin perfusion in dependency on insulinemia in healthy subjects.METHODS:All volunteers were informed in detail about the procedures and signed informed consent.The protocol of this study was approved by the ethical committee.In our study,a two stage hyperinsulinemic euglycemic clamp was performed,with insulinemia 100and 250 mIU/mL and glycemia 5.0 mmol/L(3%standard deviation).Before the clamp and in steady states,microcirculation was measured by laser Doppler flowmetry and transcutaneous oximetry and energy expenditure was measured by indirect calorimetry.Results(average and standard deviation)were evaluated with pairedt-test.RESULTS:Physiological(50 mIU/L)insulinemia led to higher perfusion in both tests;hyperemia after heating to 44%-1848%(984-2046)vs 1599%(801-1836),P<0.05,half time of reaching peak perfusion after occlusion release 1.2 s(0.9-2.6)vs 4.9 s(1.8-11.4),P<0.05.Supraphysiological(150 mIU/L)insulinemia led to even higher perfusion in both tests;hyperemia after heating to 44%-1937%(1177-2488)vs 1599%(801-1836),P<0.005,half time to reach peak perfusion after occlusion release 1.0 s(0.7-1.1)vs 4.9 s(1.8-11.4),P<0.005.A statistically significant increase occurred in tissue oxygenation in both insulinemia.The difference in perfusion and oxygenation between physiological and supraphysiological hyperinsulinemia was not statistically significant.CONCLUSION:The post occlusive hyperemia test in accordance with heating test showed significantly increasing skin perfusion in the course of artificial hyperinsulinemia.This effect rises non-linearly with increasing insulinemia.Dependency on the dose was not statistically significant.展开更多
Estrogens and artificial progestins used in hormone replacement therapy increase breast cancer risk. This seems to bedue to a promoting and not initiating effect. A synergic effect of estradiol and hyperinsulinism has...Estrogens and artificial progestins used in hormone replacement therapy increase breast cancer risk. This seems to bedue to a promoting and not initiating effect. A synergic effect of estradiol and hyperinsulinism has been shown. Insulinplays a role in the increase of breast cancer risk when associated with android obesity, sedentariness, type II diabetes,and high glycemic index food, alcohol and trans fatty acids intake. Natural menopause induces insulin resistance anddoes not induce a risk decrease. The role of insulin gives a new outlook on the influence of HRT in breast cancer promotion:estradiol alone, which improves insulin-sensitivity, does not increase breast cancer risk. Artificial progestinsassociated with estrogens increase the risk, whereas estrogens associated with progesterone do not. This could be dueto the fact that artificial progestins increase insulin resistance, whereas natural progesterone does not. Adipose tissue,which is an endocrine gland, is insulin dependant. Breast cancer and its seriousness are correlated to adipocytokincirculating levels such as resistin, leptin, interleukin 1, adipocyte fatty acid-binding protein, and are inversely correlatedto the level of adiponectin. Insulin could play a synergic role with sexual steroids by a direct effect and by increasingadipose tissue secretions.展开更多
To determine whether insulin exerts an effect on milk fat yield through the direct regulation of milk fat synthesis in the mammary gland, the hyperinsulinemic-euglycemic clamp procedure was performed in lactating goat...To determine whether insulin exerts an effect on milk fat yield through the direct regulation of milk fat synthesis in the mammary gland, the hyperinsulinemic-euglycemic clamp procedure was performed in lactating goats in the present study. The effects of the hyperinsulinemic-euglycemic clamp on milk yield, milk composition, milk fatty acid yield and the expression levels of mRNAs of milk fat synthesis-related genes were examined. The results revealed that the hyperinsulinemiceuglycemic clamp had no significant effect on the milk yield, the milk protein yield, the yield and content of lactose or the yield and content of solids-not-fat (SNF) (P > 0.05). In contrast, the milk fat percentage and milk fat yield were decreased by 35.3% and 33.6%, respectively (P < 0.01). Among the 19 fatty acids examined, the yields of 9 fatty acids were significantly reduced (P < 0.05) following the clamp procedure, including C16:0 (hexadecanoic acid), 3 fatty acids derived from blood (>C16) and 5 fatty acids synthesized de novo in the mammary gland ( 0.05), including acetyl-coenzyme A carboxylase (ACC), fatty acid synthase (FAS), fatty acidbinding protein (FABP), lipoprotein lipase (LPL), stearoyl-CoA desaturase (SCD) and glycerol-3-phosphate acyltransferase (GPAT). However, the expression level of the SCD gene was significantly reduced during the post-procedure period (P < 0.05) but returned to a normal level at 48 h after termination of the clamp procedure. It was concluded that the hyperinsulinemic-euglycemic clamp exerted a direct effect on milk fatty acid desaturation.展开更多
Objective: To observe the effect of acupuncture on hyperleptinaemia and hyperinsulinemia for studying its underlying mechanism about anti-obesity and reducing blood lipid in obesity rats. Methods: A total of 80 SD rat...Objective: To observe the effect of acupuncture on hyperleptinaemia and hyperinsulinemia for studying its underlying mechanism about anti-obesity and reducing blood lipid in obesity rats. Methods: A total of 80 SD rats were randomized into normal control, model, acupuncture and medication groups, with 20 cases in each group. Hypothalamic obesity model was established by subcutaneous injection of 15% sodium glutamate (0.2 mL/10 g body weight), once daily and continuously for 5 days. “Zusanli” (足三里 ST 36), “Sanyinjiao”(三阴交 SP 6), “Guanyuan”(关元 CV 4) and “Zhongwan”(中脘 CV 12) were punctured and stimulated electrically (100 Hz, dense-sparse waves, and a suitable strength inducing local muscular tremor) for 15 min, once daily. In medication group, rats were fed with Sibutramine 4 mg/kg, once daily. After 4 weeks’ treatment, Lee’s index was detected, and serum leptin and insulin contents were determined by radioimmunoassay (RIA). Results: Compared with normal control group, Lee’s index, serum leptin and insulin contents of model group increased significantly (P<0.01). Comparison between acupuncture and model groups, Lee’s index and serum leptin of acupuncture group decreased significantly (P<0.01), and serum insulin level also lowered. In comparison with model group, Lee’s index, serum leptin and insulin levels of medication group also lowered. Comparison between acupuncture and medication groups showed that Lee’s index and serum leptin level of acupuncture group were significantly lower than those of the later group (P<0.01), displaying that the therapeutic effect of acupuncture is better than that of Sibutramine in lowering Lee’s index and serum leptin. No significant differences were found between acupuncture and medication groups in body weight and length and serum insulin(P>0.05). Conclusion: Acupuncture can effectively reduce Lee’s index, serum leptin and insulin contents in fasting obese rats, which may contribute to its effect in anti-obesity.展开更多
Type 2 diabetes mellitus(T2DM)was identified as the most prevalent form of diabetes.This study employed an integrated strategy combining network pharmacology,metabolomics,and experimental validation to elucidate the t...Type 2 diabetes mellitus(T2DM)was identified as the most prevalent form of diabetes.This study employed an integrated strategy combining network pharmacology,metabolomics,and experimental validation to elucidate the therapeutic mechanisms of red mulberry water extract(RMW)in T2DM.Systematic analysis identified six bioactive constituents,with four key components(cyanidin,quercetin,morin,andβ-carotene)demonstrating significant interactions with diabetes-related targets.Network pharmacology revealed these compounds modulate critical pathways including AMPK(P=2.3×10^(−5)),PI3K-Akt(P=1.8×10^(−4)),and PPAR signaling(P=3.1×10^(−3)).In diabetic mice,treatment significantly improved glycemic control(32.5%reduction in fasting glucose,P<0.01),lipid profiles(36.7%lower TG,P<0.05),antioxidant activity(2.1-fold increased SOD,P<0.05),and inflammation(42%reduced TNF-α,P<0.05).Metabolomic analysis further confirmed alterations in catecholamine and lipid metabolism pathways.These findings collectively demonstrate mulberry's multi-target therapeutic potential through synergistic regulation of glucose metabolism,lipid homeostasis,oxidative stress,and inflammatory responses in diabetes.展开更多
Brain insulin resistance(BIR)is a prevalent detrimental feature of Alzheimer’s disease(AD)and all-cause dementia.Therapies designed to activate insulin signaling and enhance insulin receptor sensitivity have proven b...Brain insulin resistance(BIR)is a prevalent detrimental feature of Alzheimer’s disease(AD)and all-cause dementia.Therapies designed to activate insulin signaling and enhance insulin receptor sensitivity have proven beneficial for cognitive enhancement in pre-clinical models,non-human primates,and humans.BIR encompasses dysregulated brain insulin signaling,which is either due to insulin receptor resistance,reduced insulin receptor levels,or reduced levels of insulin in the brain,affecting processes involved in AD development and progression.展开更多
Type 2 diabetes mellitus has central complications:Diabetes,a metabolic disorder primarily characterized by hyperglycemia due to insufficient insulin secretion,or impaired insulin signaling,has significant central com...Type 2 diabetes mellitus has central complications:Diabetes,a metabolic disorder primarily characterized by hyperglycemia due to insufficient insulin secretion,or impaired insulin signaling,has significant central complications.Type 2 diabetes mellitus(T2DM),the most prevalent type of diabetes,affects more than 38 million individuals in the United States(approximately 1 in 10)and is defined by chronic hyperglycemia and insulin resistance,which refers to a reduced cellular response to insulin.展开更多
The increasing prevalence of metabolic disorders and neurodegenerative diseases has uncovered shared pathophysiological pathways,with insulin resistance and mitochondrial dysfunction emerging as critical contributors ...The increasing prevalence of metabolic disorders and neurodegenerative diseases has uncovered shared pathophysiological pathways,with insulin resistance and mitochondrial dysfunction emerging as critical contributors to cognitive decline.Insulin resistance impairs neuronal metabolism and synaptic function,fostering neurodegeneration as observed in Alzheimer’s disease and Down syndrome.Indeed,Down syndrome,characterized by the triplication of the APP gene,represents a valuable genetic model for studying early-onset Alzheimer’s disease and accelerated aging.Building on the link between metabolic dysfunctions and neurodegeneration,innovative strategies addressed brain insulin resistance as a key driver of cognitive decline.Intranasal insulin has shown promise in improving cognition in early Alzheimer’s disease and type 2 diabetes,supporting the concept that restoring insulin sensitivity can mitigate neurodegeneration.However,insulin-based therapies risk desensitizing insulin signaling,potentially worsening the disease.Incretins,particularly glucagon-like peptide 1 receptor agonists,offer neuroprotective benefits by enhancing insulin sensitivity,metabolism,and synaptic plasticity while reducing oxidative distress and neuroinflammation.This review focuses on current knowledge on the metabolic and molecular interactions between insulin resistance,mitochondrial dynamics(including their roles in energy metabolism),and oxidative distress regulation,as these are pivotal in both Alzheimer’s disease and Down syndrome.By addressing these interconnected mechanisms,innovative treatments may emerge for both metabolic and neurodegenerative disorders.展开更多
Brain-specific serine/threonine-protein kinase 2(BRSK2)plays critical roles in insulin secretion andβ-cell biology.However,whether BRSK2 is associated with human type 2 diabetes mellitus(T2DM)has not been determined....Brain-specific serine/threonine-protein kinase 2(BRSK2)plays critical roles in insulin secretion andβ-cell biology.However,whether BRSK2 is associated with human type 2 diabetes mellitus(T2DM)has not been determined.Here,we report that BRSK2 genetic variants are closely related to worsening glucose metabolism due to hyperinsulinemia and insulin resistance in the Chinese population.BRSK2 protein levels are significantly elevated inβcells from T2DM patients and high-fat diet(HFD)-fed mice due to enhanced protein stability.Mice with inducibleβ-cell-specific Brsk2 knockout(βKO)exhibit normal metabolism with a high potential for insulin secretion under chow-diet conditions.Moreover,βKO mice are protected from HFD-induced hyperinsulinemia,obesity,insulin resistance,and glucose intolerance.Conversely,gain-of-function BRSK2 in matureβcells reversibly triggers hyperglycemia due toβ-cell hypersecretion-coupled insulin resistance.Mechanistically,BRSK2 senses lipid signals and induces basal insulin secretion in a kinase-dependent manner.The enhanced basal insulin secretion drives insulin resistance andβ-cell exhaustion and thus the onset of T2DM in mice fed an HFD or with gain-of-function BRSK2 inβcells.These findings reveal that BRSK2 links hyperinsulinemia to systematic insulin resistance via interplay betweenβcells and insulin-sensitive tissues in the populations carrying human genetic variants or under nutrient-overload conditions.展开更多
Diabetes mellitus(DM)is a global health challenge with increasing prevalence rates,particularly in low-and middle-income countries.Anthocyanins(ACs)are potential bioactive compounds found in various fruits and vegetab...Diabetes mellitus(DM)is a global health challenge with increasing prevalence rates,particularly in low-and middle-income countries.Anthocyanins(ACs)are potential bioactive compounds found in various fruits and vegetables,attracting the attention of researchers due to their possible role in managing diabetes and its complications.Studies have demonstrated the beneficial effects of ACs on blood sugar levels,insulin sensitivity,and glucose tolerance.These effects may be associated with multiple mechanisms,including increased glucose transporter type 4(GLUT4)expression,enhanced glucose uptake,AMP-activated protein kinase(AMPK)and protein kinase C(PKC)phosphorylation,improved insulin sensitivity,activation of phosphoinositide 3-kinase/protein kinase B(PI3K/AKT)signaling,increased glutathione(GSH)synthesis,production of short-chain fatty acids(SCFAs),glucagon-like peptide-1(GLP-1)secretion,induction of antioxidant enzymes,improved beta-cell functioning,and activation of insulin signaling pathways.The activity of enzymes(alpha amylase,glucosidase,and dipeptidyl peptidase-IV[DPP-IV])and the expression of inflammatory biomarkers(tumor necrosis factor[TNF],IL6,and MCP1)are reduced.These findings suggest the potential of ACs as adjunctive therapies.However,further studies,including well-structured clinical trials,are needed to explore the optimal dosage and long-term efficacy of ACs in diabetes management.展开更多
There is increasing interest in developing reduced-crude protein(CP)diets for broiler chickens because their commercial adoption would generate a diverse range of advantages that would enhance the sustainability of th...There is increasing interest in developing reduced-crude protein(CP)diets for broiler chickens because their commercial adoption would generate a diverse range of advantages that would enhance the sustainability of the chickenmeat industry.However,the development of reduced-CP broiler diets is proving to be not straightforward,particularly when dietary CP reductions exceed 30 g/kg.The capacity of broilers to accommodate dietary CP reductions when offered maize-based diets is superior to their counterparts offered wheat-based diets.Numerous factors could be contributing to this difference but have yet to be identified with certainty.Maize-based,reduced-CP diets characteristically support better weight gains and efficiencies of feed conversion than wheat-based diets,but this better growth performance is associated with increased fat deposition,monitored as heavier relative abdominal fat-pad weights.This is an intriguing dichotomy.Insulin is a powerful anabolic hormone in mammalian species capable of promoting fat deposition,protein accretion and growth,but the importance of insulin in avian species is usually dismissed.This is because broiler chickens are considered both hyperglycaemic and resistant to insulin.However,the likelihood is that young broiler chickens are more sensitive to insulin than is generally recognised and the anabolic properties of insulin may be contributing to the diverse responses observed between maize and wheat in the context of reduced-CP diets.Dietary CP reductions may trigger increased plasma ammonia concentrations and metabolic acidosis,but both factors can influence insulin secretion and insulin resistance.Maize has slower rates of starch digestion and glucose absorption than wheat and it has been suggested that this generates a more sustained insulin release resulting in increased weight gains and fat deposition.If so,this could be driving the differences generated by the feed grain selected as the basis of reduced-CP diets.The intention of this review is to explore this proposition because if the causal factors of the differences between maize and wheat can be identified the development and acceptance of reduced-CP broiler diets should be accelerated.展开更多
Background The phenomenon where excessive activation of branched-chain amino acid(BCAA)degrading enzymes caused by high concentrations of leucine(Leu)leads to a decrease in the overall concentration of BCAA[including ...Background The phenomenon where excessive activation of branched-chain amino acid(BCAA)degrading enzymes caused by high concentrations of leucine(Leu)leads to a decrease in the overall concentration of BCAA[including isoleucine(Ile)and valine(Val)]is called BCAA antagonism.Although this phenomenon has long been widely studied,the specific mechanism of its occurrence is still poorly understood.In this study,we investigated the specific mechanism by which Val and Ile alleviate the antagonistic effect caused by high concentrations of Leu through influencing insulin function.First,the ratios of Ile and Val in the low-protein diet were adjusted up and down by 15%to observe the metabolic status of broilers at the end of the experiment(the experiment period was from 0 to 42 d).Subsequently,the physiological and biochemical changes related to antagonism were determined using transcriptome and lipid metabolome analyses.Results When fed with a high concentration of Leu,restricting Ile or supplementing Val can effectively alleviate antagonism.Under conditions of excessive dietary Val supplementation,insulin levels remained stable,whereas blood glucose levels increased(P<0.05),and liver fat accumulated predominantly as ceramides rather than triglycerides,thereby disrupting the insulin-mediated phosphatidylinositol 3-kinase/protein kinase B signaling pathway(P<0.05).Excessive dietary Ile promoted liver inflammation and interleukin-6 release(P<0.05),which acted on the pancreas to enhance insulin secretion.Additionally,the glucagon content in the pancreas decreased(P<0.05),while insulin and glucagon-like peptide-1 levels increased(P<0.05).Conclusion Supplementation of Val or restriction of Ile in low-protein diets could alleviate the BCAA antagonism caused by high Leu,which mainly achieved by influencing insulin function.These findings provide new insights in revealing the BCAA antagonism.展开更多
Obesity is widely recognized as a global epidemic,primarily driven by an imbalance between energy expenditure and caloric intake associated with a sedentary lifestyle.Diets high in carbohydrates and saturated fats,par...Obesity is widely recognized as a global epidemic,primarily driven by an imbalance between energy expenditure and caloric intake associated with a sedentary lifestyle.Diets high in carbohydrates and saturated fats,particularly palmitic acid,are potent inducers of chronic low-grade inflammation,largely due to disruptions in glucose metabolism and the onset of insulin resistance(Qiu et al.,2022).While many organs are affected,the brain,specifically the hypothalamus,is among the first to exhibit inflammation in response to an unhealthy diet,suggesting that obesity may,in fact,be a brain-centered disease with neuroinflammation as a central factor(Thaler et al., 2012).展开更多
Diabetic kidney disease (DKD)is one of the most common and severe microvascular complications of type 2 diabetes mellitus (T2DM). It is also a major cause of end-stage renal disease (ESRD), making early identification...Diabetic kidney disease (DKD)is one of the most common and severe microvascular complications of type 2 diabetes mellitus (T2DM). It is also a major cause of end-stage renal disease (ESRD), making early identification and intervention crucial. Insulin resistance (IR)is a key pathophysiological mechanism of T2DM and plays a central role in the progression of DKD. In recent years, a series of novel surrogate indicators of IR, such as the triglyceride-glucose (TyG) index, TyG-body mass index (TyG-BMI), triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C), and metabolic score for insulin resistance (METS-IR), have attracted widespread attention due to their simplicity and cost-effectiveness. This article reviews the research progress of novel surrogate indicators of insulin resistance (IR) in type 2 diabetic kidney disease (DKD), aiming to provide references for the early prevention and improved prognosis of DKD.展开更多
Diabetes is accompanied by oxidative damage,inflammation,and disorder of metabolic profiles.Dietary procyanidins have been reported to alleviate symptoms of diabetes,however,the underlying mechanism through which proc...Diabetes is accompanied by oxidative damage,inflammation,and disorder of metabolic profiles.Dietary procyanidins have been reported to alleviate symptoms of diabetes,however,the underlying mechanism through which procyanidins impact liver metabolic function remains unclear.Here,the effects of p eanut skin procyanidins(PSP)on oxidative stress,inflammatory injury,and dysregulated metabolism in the liver of diabetic mice were evaluated.The results showed that PSP r educed the accumulation of cholesterol and alleviated oxidative stress and inflammatory response in the liver.Moreover,PSP enhanced i nsulin signaling by increasing hepatic protein expression of insulin receptor substrate 1/phosphatidylinositol-3-kinase/protein kinase B.Untargeted metabolomics revealed that PSP altered bile acid biosynthesis,alpha linolenic acid and linoleic acid,arachidonic acid,and glycolipid metabolism in the liver.This study reveals positive effects of PSP in alleviating liver dysfunction in diabetic mice.展开更多
基金supported by the Medical College Natural Science Foundation of Shanghai Jiao Tong University (09XJ21028)the Shanghai Jiaotong University Interdisciplinary Study Foundation Medicine and Engineer
文摘Objective decline of resistance whether H Type 2 diabetes has been recently recognized as an important risk factor for cognitive patients with Alzheimer＇s disease （AD）. But the roles of hyperinsulinemia （HI） and insulin （IR） in the development of AD are still controversial. This study was designed to evaluate or IR influenced the cognitive functions of older cohort. Methods The cognitive functions of 328 consecutive elderly patients were evaluated with a battery of cognitive rating scales. Their fasting blood glucose （FBG） and fasting insulin （FINS） were analyzed and IR was calculated with modified-Homa. The cognitive scores in different groups and the correlation of cognitive functions with HI or IR were analyzed. Results In our study, there were 180 participants with HI and 148 without HI, and 192 with iR and 136 without IR. The participants with HI showed worse cognitive functions than those without HI in MMSE, MOCA, CDR, orientation, delayed memory, and attention/calculation domains. Similarly, the elderly with IR had lower cognitive scores than those without IR in MMSE, MOCA, CDR, GDS, orientation, delayed memory, and attention/calculation domains. The insulin levels and Homa IR had negative correlation with the scores of MMSE and delayed memory, not only in the model I adjusted for FBG and diabetes history, but also in the model 2 adjusted for all nine demographic characteristics. Conclusion HI and IR are important risk factors for cognitive decline of the elderly, especially for the dysfunctions in delayed memory domains.
文摘Nutritional supplementation has long been studied as a possible treatment alternative or as an adjunct to the standard treatments for common ailments and diseases.According to the latest research,the Chilean maqui berry,Aristotelia chilensis,has been shown to reduce postprandial insulin levels by as much as fifty percent.The berry,which has been shown to be as effective as metformin at increasing insulin sensitivity and controlling blood glucose levels,follows a simple mechanism of action that involves the inhibition of sodium dependent glucose transporters in the small intestine,slowing the rate at which sugars enter the bloodstream and thereby decreasing blood sugar spikes and the corresponding increase in insulin levels.Chronically high blood glucose levels have been proven to play a significant role in the development of cancers,as diabetics and prediabetics have been proven to have elevated risk of developing cancerous growth.Consistent dietary supplementation with maqui berry may therefore indirectly reduce the risk of cancer,as well as other diseases which respond negatively to hyperglycemia and hyperinsulinemia.
基金The Grant of National Center for Global Health and Medicine, No. 22-120
文摘Inflammation induces insulin resistance and hyperinsulinemia due to elevation of serum cytokines such as tumor necrosis factor-α and interleukins. Chronic myeloproliferative diseases including myelofibrosis show higher serum interleukin levels than healthy subjects, which has been suggested to be the useful markers for disease activity. However, an association between myelofibrosis and insulin resistance has not ever been discussed anywhere. Here we report a case of type 2 diabetes showing remarkable hyperinsulinemia and insulin resistance possibly due to myelofibrosis.
文摘Backgrounds: Differences in serum lipids profiles in different type of glucose intolerance are unclear. Aims: To characterize lipid profiles in different type of glucose intolerance, and to assess relationships between serum lipids profile and disturbance of glucose metabolism in prediabetic subjects. Methods: Using the measurements in medical check-up with 75 goral glucose tolerance test (OGTT), total of 620 male subjects, who are not on medications for metabolic diseases or hypertension, were divided into normal fasting glucose and glucose tolerance (NFG/ NGT), isolated impaired fasting glucose (iIFG), isolated impaired glucose tolerance (iIGT) and combined IFG and IGT (IFG/IGT) based on results of the OGTT. Results: Age and body mass index (BMI) were similar in the four groups. Matsuda index (an index of whole body insulin sensitivity) was lower in iIFG, iIGT and IFG/IGT as compared with NFG/NGT. Plasma insulin excursion during the OGTT was significantly higher in IFG/IGT versus NFG/NGT. Serum triglyceride level (TG) and TG to HDL ratio (TG/HDL) were higher in IFG/IGT versus NFG/NGT. Matsuda index was positively correlated with HDL and was inversely correlated with TG, LDL, non-HDL, TG/ HDL and LDL to HDL ratio (LDL/HDL). Backward stepwise multiple regression analysis indicated that increases in BMI, plasma insulin level at 60 min (PI60) and plasma glucose level at 120 min in the OGTT were independently associated with increases in TG and TG/HDL. Increases in BMI and PI60 were related to an increase in non-HDL and LDL/HDL and a decrease in HDL. Conclusions: These results indicate that postprandial hyperglycemia and hyperinsulinemia based on advanced insulin resistance are closely related to lipid risk factors of atherosclerotic macrovascular disease in prediabetic subjects.
基金Supported by Ministry of Health,Czech Republic-Conceptual Development of Research Organization(Faculty Hospital in Pilsen-FNPl),No.00669806
文摘AIM:To examine skin perfusion in dependency on insulinemia in healthy subjects.METHODS:All volunteers were informed in detail about the procedures and signed informed consent.The protocol of this study was approved by the ethical committee.In our study,a two stage hyperinsulinemic euglycemic clamp was performed,with insulinemia 100and 250 mIU/mL and glycemia 5.0 mmol/L(3%standard deviation).Before the clamp and in steady states,microcirculation was measured by laser Doppler flowmetry and transcutaneous oximetry and energy expenditure was measured by indirect calorimetry.Results(average and standard deviation)were evaluated with pairedt-test.RESULTS:Physiological(50 mIU/L)insulinemia led to higher perfusion in both tests;hyperemia after heating to 44%-1848%(984-2046)vs 1599%(801-1836),P<0.05,half time of reaching peak perfusion after occlusion release 1.2 s(0.9-2.6)vs 4.9 s(1.8-11.4),P<0.05.Supraphysiological(150 mIU/L)insulinemia led to even higher perfusion in both tests;hyperemia after heating to 44%-1937%(1177-2488)vs 1599%(801-1836),P<0.005,half time to reach peak perfusion after occlusion release 1.0 s(0.7-1.1)vs 4.9 s(1.8-11.4),P<0.005.A statistically significant increase occurred in tissue oxygenation in both insulinemia.The difference in perfusion and oxygenation between physiological and supraphysiological hyperinsulinemia was not statistically significant.CONCLUSION:The post occlusive hyperemia test in accordance with heating test showed significantly increasing skin perfusion in the course of artificial hyperinsulinemia.This effect rises non-linearly with increasing insulinemia.Dependency on the dose was not statistically significant.
文摘Estrogens and artificial progestins used in hormone replacement therapy increase breast cancer risk. This seems to bedue to a promoting and not initiating effect. A synergic effect of estradiol and hyperinsulinism has been shown. Insulinplays a role in the increase of breast cancer risk when associated with android obesity, sedentariness, type II diabetes,and high glycemic index food, alcohol and trans fatty acids intake. Natural menopause induces insulin resistance anddoes not induce a risk decrease. The role of insulin gives a new outlook on the influence of HRT in breast cancer promotion:estradiol alone, which improves insulin-sensitivity, does not increase breast cancer risk. Artificial progestinsassociated with estrogens increase the risk, whereas estrogens associated with progesterone do not. This could be dueto the fact that artificial progestins increase insulin resistance, whereas natural progesterone does not. Adipose tissue,which is an endocrine gland, is insulin dependant. Breast cancer and its seriousness are correlated to adipocytokincirculating levels such as resistin, leptin, interleukin 1, adipocyte fatty acid-binding protein, and are inversely correlatedto the level of adiponectin. Insulin could play a synergic role with sexual steroids by a direct effect and by increasingadipose tissue secretions.
文摘To determine whether insulin exerts an effect on milk fat yield through the direct regulation of milk fat synthesis in the mammary gland, the hyperinsulinemic-euglycemic clamp procedure was performed in lactating goats in the present study. The effects of the hyperinsulinemic-euglycemic clamp on milk yield, milk composition, milk fatty acid yield and the expression levels of mRNAs of milk fat synthesis-related genes were examined. The results revealed that the hyperinsulinemiceuglycemic clamp had no significant effect on the milk yield, the milk protein yield, the yield and content of lactose or the yield and content of solids-not-fat (SNF) (P > 0.05). In contrast, the milk fat percentage and milk fat yield were decreased by 35.3% and 33.6%, respectively (P < 0.01). Among the 19 fatty acids examined, the yields of 9 fatty acids were significantly reduced (P < 0.05) following the clamp procedure, including C16:0 (hexadecanoic acid), 3 fatty acids derived from blood (>C16) and 5 fatty acids synthesized de novo in the mammary gland ( 0.05), including acetyl-coenzyme A carboxylase (ACC), fatty acid synthase (FAS), fatty acidbinding protein (FABP), lipoprotein lipase (LPL), stearoyl-CoA desaturase (SCD) and glycerol-3-phosphate acyltransferase (GPAT). However, the expression level of the SCD gene was significantly reduced during the post-procedure period (P < 0.05) but returned to a normal level at 48 h after termination of the clamp procedure. It was concluded that the hyperinsulinemic-euglycemic clamp exerted a direct effect on milk fatty acid desaturation.
文摘Objective: To observe the effect of acupuncture on hyperleptinaemia and hyperinsulinemia for studying its underlying mechanism about anti-obesity and reducing blood lipid in obesity rats. Methods: A total of 80 SD rats were randomized into normal control, model, acupuncture and medication groups, with 20 cases in each group. Hypothalamic obesity model was established by subcutaneous injection of 15% sodium glutamate (0.2 mL/10 g body weight), once daily and continuously for 5 days. “Zusanli” (足三里 ST 36), “Sanyinjiao”(三阴交 SP 6), “Guanyuan”(关元 CV 4) and “Zhongwan”(中脘 CV 12) were punctured and stimulated electrically (100 Hz, dense-sparse waves, and a suitable strength inducing local muscular tremor) for 15 min, once daily. In medication group, rats were fed with Sibutramine 4 mg/kg, once daily. After 4 weeks’ treatment, Lee’s index was detected, and serum leptin and insulin contents were determined by radioimmunoassay (RIA). Results: Compared with normal control group, Lee’s index, serum leptin and insulin contents of model group increased significantly (P<0.01). Comparison between acupuncture and model groups, Lee’s index and serum leptin of acupuncture group decreased significantly (P<0.01), and serum insulin level also lowered. In comparison with model group, Lee’s index, serum leptin and insulin levels of medication group also lowered. Comparison between acupuncture and medication groups showed that Lee’s index and serum leptin level of acupuncture group were significantly lower than those of the later group (P<0.01), displaying that the therapeutic effect of acupuncture is better than that of Sibutramine in lowering Lee’s index and serum leptin. No significant differences were found between acupuncture and medication groups in body weight and length and serum insulin(P>0.05). Conclusion: Acupuncture can effectively reduce Lee’s index, serum leptin and insulin contents in fasting obese rats, which may contribute to its effect in anti-obesity.
文摘Type 2 diabetes mellitus(T2DM)was identified as the most prevalent form of diabetes.This study employed an integrated strategy combining network pharmacology,metabolomics,and experimental validation to elucidate the therapeutic mechanisms of red mulberry water extract(RMW)in T2DM.Systematic analysis identified six bioactive constituents,with four key components(cyanidin,quercetin,morin,andβ-carotene)demonstrating significant interactions with diabetes-related targets.Network pharmacology revealed these compounds modulate critical pathways including AMPK(P=2.3×10^(−5)),PI3K-Akt(P=1.8×10^(−4)),and PPAR signaling(P=3.1×10^(−3)).In diabetic mice,treatment significantly improved glycemic control(32.5%reduction in fasting glucose,P<0.01),lipid profiles(36.7%lower TG,P<0.05),antioxidant activity(2.1-fold increased SOD,P<0.05),and inflammation(42%reduced TNF-α,P<0.05).Metabolomic analysis further confirmed alterations in catecholamine and lipid metabolism pathways.These findings collectively demonstrate mulberry's multi-target therapeutic potential through synergistic regulation of glucose metabolism,lipid homeostasis,oxidative stress,and inflammatory responses in diabetes.
文摘Brain insulin resistance(BIR)is a prevalent detrimental feature of Alzheimer’s disease(AD)and all-cause dementia.Therapies designed to activate insulin signaling and enhance insulin receptor sensitivity have proven beneficial for cognitive enhancement in pre-clinical models,non-human primates,and humans.BIR encompasses dysregulated brain insulin signaling,which is either due to insulin receptor resistance,reduced insulin receptor levels,or reduced levels of insulin in the brain,affecting processes involved in AD development and progression.
基金supported by grants from NIH T32(DK007260,to WC)the Steno North American Fellowship awarded by the Novo Nordisk Foundation(NNF23OC0087108,to WC)+6 种基金STI2030-Major Projects(2021ZD0202700,to HY)the National Natural Science Foundation of China(32241004,to HY)the Natural Science Foundation of Zhejiang Province of China(LR24C090001,to HY)Key R&D Program of Zhejiang Province(2024SSYS0017,to HY)CAMS Innovation Fund for Medical Sciences(2019-12M-5-057,to HY)Fundamental Research Funds for the Central Universities(226-2022-00193,to HY)the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2023-PT310-01,to HY)。
文摘Type 2 diabetes mellitus has central complications:Diabetes,a metabolic disorder primarily characterized by hyperglycemia due to insufficient insulin secretion,or impaired insulin signaling,has significant central complications.Type 2 diabetes mellitus(T2DM),the most prevalent type of diabetes,affects more than 38 million individuals in the United States(approximately 1 in 10)and is defined by chronic hyperglycemia and insulin resistance,which refers to a reduced cellular response to insulin.
基金supported by Fondi Ateneo grants funded by Sapienza University (#RM120172A3160B53) to EBfunds from Jerome-Lejeune Foundation (#1887-2019b) to EBthe European Union–Next Generation EU (Project ECS 0000024Rome Technopole,–CUP B83C22002820006, NRPMission 4 Component 2 Investment 1.5 to LRR)
文摘The increasing prevalence of metabolic disorders and neurodegenerative diseases has uncovered shared pathophysiological pathways,with insulin resistance and mitochondrial dysfunction emerging as critical contributors to cognitive decline.Insulin resistance impairs neuronal metabolism and synaptic function,fostering neurodegeneration as observed in Alzheimer’s disease and Down syndrome.Indeed,Down syndrome,characterized by the triplication of the APP gene,represents a valuable genetic model for studying early-onset Alzheimer’s disease and accelerated aging.Building on the link between metabolic dysfunctions and neurodegeneration,innovative strategies addressed brain insulin resistance as a key driver of cognitive decline.Intranasal insulin has shown promise in improving cognition in early Alzheimer’s disease and type 2 diabetes,supporting the concept that restoring insulin sensitivity can mitigate neurodegeneration.However,insulin-based therapies risk desensitizing insulin signaling,potentially worsening the disease.Incretins,particularly glucagon-like peptide 1 receptor agonists,offer neuroprotective benefits by enhancing insulin sensitivity,metabolism,and synaptic plasticity while reducing oxidative distress and neuroinflammation.This review focuses on current knowledge on the metabolic and molecular interactions between insulin resistance,mitochondrial dynamics(including their roles in energy metabolism),and oxidative distress regulation,as these are pivotal in both Alzheimer’s disease and Down syndrome.By addressing these interconnected mechanisms,innovative treatments may emerge for both metabolic and neurodegenerative disorders.
基金supported by research grants from the National Natural Science Foundation of China(81420108007 and 81830024 to X.H.,82270844,82070843,and 81870531 to Y.Zhu).
文摘Brain-specific serine/threonine-protein kinase 2(BRSK2)plays critical roles in insulin secretion andβ-cell biology.However,whether BRSK2 is associated with human type 2 diabetes mellitus(T2DM)has not been determined.Here,we report that BRSK2 genetic variants are closely related to worsening glucose metabolism due to hyperinsulinemia and insulin resistance in the Chinese population.BRSK2 protein levels are significantly elevated inβcells from T2DM patients and high-fat diet(HFD)-fed mice due to enhanced protein stability.Mice with inducibleβ-cell-specific Brsk2 knockout(βKO)exhibit normal metabolism with a high potential for insulin secretion under chow-diet conditions.Moreover,βKO mice are protected from HFD-induced hyperinsulinemia,obesity,insulin resistance,and glucose intolerance.Conversely,gain-of-function BRSK2 in matureβcells reversibly triggers hyperglycemia due toβ-cell hypersecretion-coupled insulin resistance.Mechanistically,BRSK2 senses lipid signals and induces basal insulin secretion in a kinase-dependent manner.The enhanced basal insulin secretion drives insulin resistance andβ-cell exhaustion and thus the onset of T2DM in mice fed an HFD or with gain-of-function BRSK2 inβcells.These findings reveal that BRSK2 links hyperinsulinemia to systematic insulin resistance via interplay betweenβcells and insulin-sensitive tissues in the populations carrying human genetic variants or under nutrient-overload conditions.
文摘Diabetes mellitus(DM)is a global health challenge with increasing prevalence rates,particularly in low-and middle-income countries.Anthocyanins(ACs)are potential bioactive compounds found in various fruits and vegetables,attracting the attention of researchers due to their possible role in managing diabetes and its complications.Studies have demonstrated the beneficial effects of ACs on blood sugar levels,insulin sensitivity,and glucose tolerance.These effects may be associated with multiple mechanisms,including increased glucose transporter type 4(GLUT4)expression,enhanced glucose uptake,AMP-activated protein kinase(AMPK)and protein kinase C(PKC)phosphorylation,improved insulin sensitivity,activation of phosphoinositide 3-kinase/protein kinase B(PI3K/AKT)signaling,increased glutathione(GSH)synthesis,production of short-chain fatty acids(SCFAs),glucagon-like peptide-1(GLP-1)secretion,induction of antioxidant enzymes,improved beta-cell functioning,and activation of insulin signaling pathways.The activity of enzymes(alpha amylase,glucosidase,and dipeptidyl peptidase-IV[DPP-IV])and the expression of inflammatory biomarkers(tumor necrosis factor[TNF],IL6,and MCP1)are reduced.These findings suggest the potential of ACs as adjunctive therapies.However,further studies,including well-structured clinical trials,are needed to explore the optimal dosage and long-term efficacy of ACs in diabetes management.
基金Australian Research Council Linkage project(LP220100292)for partially supporting Mengzhu Wang’s PhD scholarship。
文摘There is increasing interest in developing reduced-crude protein(CP)diets for broiler chickens because their commercial adoption would generate a diverse range of advantages that would enhance the sustainability of the chickenmeat industry.However,the development of reduced-CP broiler diets is proving to be not straightforward,particularly when dietary CP reductions exceed 30 g/kg.The capacity of broilers to accommodate dietary CP reductions when offered maize-based diets is superior to their counterparts offered wheat-based diets.Numerous factors could be contributing to this difference but have yet to be identified with certainty.Maize-based,reduced-CP diets characteristically support better weight gains and efficiencies of feed conversion than wheat-based diets,but this better growth performance is associated with increased fat deposition,monitored as heavier relative abdominal fat-pad weights.This is an intriguing dichotomy.Insulin is a powerful anabolic hormone in mammalian species capable of promoting fat deposition,protein accretion and growth,but the importance of insulin in avian species is usually dismissed.This is because broiler chickens are considered both hyperglycaemic and resistant to insulin.However,the likelihood is that young broiler chickens are more sensitive to insulin than is generally recognised and the anabolic properties of insulin may be contributing to the diverse responses observed between maize and wheat in the context of reduced-CP diets.Dietary CP reductions may trigger increased plasma ammonia concentrations and metabolic acidosis,but both factors can influence insulin secretion and insulin resistance.Maize has slower rates of starch digestion and glucose absorption than wheat and it has been suggested that this generates a more sustained insulin release resulting in increased weight gains and fat deposition.If so,this could be driving the differences generated by the feed grain selected as the basis of reduced-CP diets.The intention of this review is to explore this proposition because if the causal factors of the differences between maize and wheat can be identified the development and acceptance of reduced-CP broiler diets should be accelerated.
基金financially supported by the National Key R&D Program of China(2021YFD1300404)Shenyang Governmental Science and Technology Program(Project No.22-316-2-02)+1 种基金China Agriculture Research System program(CARS-41)China Association for Science and Technology(CAST)Youth Talent Lifting Project–Special Program for Doctoral Candidates(2024)。
文摘Background The phenomenon where excessive activation of branched-chain amino acid(BCAA)degrading enzymes caused by high concentrations of leucine(Leu)leads to a decrease in the overall concentration of BCAA[including isoleucine(Ile)and valine(Val)]is called BCAA antagonism.Although this phenomenon has long been widely studied,the specific mechanism of its occurrence is still poorly understood.In this study,we investigated the specific mechanism by which Val and Ile alleviate the antagonistic effect caused by high concentrations of Leu through influencing insulin function.First,the ratios of Ile and Val in the low-protein diet were adjusted up and down by 15%to observe the metabolic status of broilers at the end of the experiment(the experiment period was from 0 to 42 d).Subsequently,the physiological and biochemical changes related to antagonism were determined using transcriptome and lipid metabolome analyses.Results When fed with a high concentration of Leu,restricting Ile or supplementing Val can effectively alleviate antagonism.Under conditions of excessive dietary Val supplementation,insulin levels remained stable,whereas blood glucose levels increased(P<0.05),and liver fat accumulated predominantly as ceramides rather than triglycerides,thereby disrupting the insulin-mediated phosphatidylinositol 3-kinase/protein kinase B signaling pathway(P<0.05).Excessive dietary Ile promoted liver inflammation and interleukin-6 release(P<0.05),which acted on the pancreas to enhance insulin secretion.Additionally,the glucagon content in the pancreas decreased(P<0.05),while insulin and glucagon-like peptide-1 levels increased(P<0.05).Conclusion Supplementation of Val or restriction of Ile in low-protein diets could alleviate the BCAA antagonism caused by high Leu,which mainly achieved by influencing insulin function.These findings provide new insights in revealing the BCAA antagonism.
文摘Obesity is widely recognized as a global epidemic,primarily driven by an imbalance between energy expenditure and caloric intake associated with a sedentary lifestyle.Diets high in carbohydrates and saturated fats,particularly palmitic acid,are potent inducers of chronic low-grade inflammation,largely due to disruptions in glucose metabolism and the onset of insulin resistance(Qiu et al.,2022).While many organs are affected,the brain,specifically the hypothalamus,is among the first to exhibit inflammation in response to an unhealthy diet,suggesting that obesity may,in fact,be a brain-centered disease with neuroinflammation as a central factor(Thaler et al., 2012).
文摘Diabetic kidney disease (DKD)is one of the most common and severe microvascular complications of type 2 diabetes mellitus (T2DM). It is also a major cause of end-stage renal disease (ESRD), making early identification and intervention crucial. Insulin resistance (IR)is a key pathophysiological mechanism of T2DM and plays a central role in the progression of DKD. In recent years, a series of novel surrogate indicators of IR, such as the triglyceride-glucose (TyG) index, TyG-body mass index (TyG-BMI), triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C), and metabolic score for insulin resistance (METS-IR), have attracted widespread attention due to their simplicity and cost-effectiveness. This article reviews the research progress of novel surrogate indicators of insulin resistance (IR) in type 2 diabetic kidney disease (DKD), aiming to provide references for the early prevention and improved prognosis of DKD.
基金supported by the project of National Natural Science Foundation of China(32272331 and 82560638)Guizhou Provincial Science and Technology Projects(Qiankehe[2024]youth 326)+1 种基金Zunyi Science and Technology Projects(Zunshikehe HZ zi 2024312 hao)Guizhou Provincial Health Commission Science and Technology Fund(gzwkj2025-512).
文摘Diabetes is accompanied by oxidative damage,inflammation,and disorder of metabolic profiles.Dietary procyanidins have been reported to alleviate symptoms of diabetes,however,the underlying mechanism through which procyanidins impact liver metabolic function remains unclear.Here,the effects of p eanut skin procyanidins(PSP)on oxidative stress,inflammatory injury,and dysregulated metabolism in the liver of diabetic mice were evaluated.The results showed that PSP r educed the accumulation of cholesterol and alleviated oxidative stress and inflammatory response in the liver.Moreover,PSP enhanced i nsulin signaling by increasing hepatic protein expression of insulin receptor substrate 1/phosphatidylinositol-3-kinase/protein kinase B.Untargeted metabolomics revealed that PSP altered bile acid biosynthesis,alpha linolenic acid and linoleic acid,arachidonic acid,and glycolipid metabolism in the liver.This study reveals positive effects of PSP in alleviating liver dysfunction in diabetic mice.
