This study investigated the effects of a xylitol-casein non-covalent complex(XC)on parameters related to type 2 diabetes mellitus(T2DM),in addition to related changes in gut microbiome composition and functions.High-f...This study investigated the effects of a xylitol-casein non-covalent complex(XC)on parameters related to type 2 diabetes mellitus(T2DM),in addition to related changes in gut microbiome composition and functions.High-fat-diet(HFD)+streptozotocin(STZ)-induced T2DM mice were treated with xylitol(XY),casein(CN),and XC,after which fecal samples were collected for gut microbiota composition and diversity analyses based on 16S rRNA high-throughput sequencing and multivariate statistics.XC decreased body weight and improved glucose tolerance,insulin sensitivity,pancreas impairment,blood lipid levels,and liver function in T2DM mice compared to XY-and CN-treated mice.Furthermore,XC modulated theα-diversity,β-diversity and gut microbiota composition.Based on Spearman’s correlation analysis,the relative abundances of Alistipes,Bacteroides,and Faecalibaculum were positively correlated and those of Akkermansia,Lactobacillus,Bifidobacterium,and Turicibacter were negatively correlated with the phenotypes related to the improvement of T2DM.In conclusion,we found that XC alleviated insulin resistance by restoring the gut microbiota of T2DM mice.Our results provide strong evidence for the beneficial effects of XC on T2DM and motivation for further investigation in animal models and,eventually,human trials.展开更多
With the prevalence of obesity and obesity-related metabolic syndrome,such as insulin resistance in recent years,it is urgent to explore effective interventions to prevent the progression of obesity-related metabolic ...With the prevalence of obesity and obesity-related metabolic syndrome,such as insulin resistance in recent years,it is urgent to explore effective interventions to prevent the progression of obesity-related metabolic syndrome.Palmitoleic acid is a monounsaturated fatty acid that is available from dietary sources,mainly derived from marine products.P almitoleic acid plays a positive role in maintaining glucose homeostasis and reducing inflammation.However,it is still unknow the mechanism of palmitoleic acid in ameliorating insulin resistance.Here,we investigated the effects of palmitoleic acid on chow diet(CD)-fed and high-fat diet(HFD)-fed mice,which were fed CD or HFD for 12 weeks before administration.We administrated mice with BSA(control),oleic acid,or palmitoleic acid for 6 weeks on top of CD or HFD feeding.We found that palmitoleic acid only improved glucose homeostasis in HFD-fed obese mice by increasing glucose clearance and reducing HOMA-IR.Further study explored that palmitoleic acid changed the composition of gut microbiota by decreasing Firmicutes population and increasing Bacteroidetes population.In colon,palmitoleic acid increased intestinal tight junction integrity and reduced inflammation.Moreover,palmitoleic acid decreased macrophage infiltration in liver and adipose tissue and increase glucose uptake in adipose tissue.Diacylglycerol(DAG)in tissue(for example,liver)is found to positively correlated with HOMA-IR.HFD enhanced the levels of DAGs in liver but not in adipose tissue in this study.Palmitoleic acid did not reverse the high DAG levels induced by HFD in liver.Therefore,in HFD-fed mice,palmitoleic acid reduced insulin resistance by an independent-manner of DAGs.It might be associated with the beneficial effects of palmitoleic acid on altering the gut microbiota composition,improving of intestinal barrier function,and downregulating the inflammation in colon,liver,and adipose tissue.展开更多
Objective To investigate the relationship between insulin resistance and carotid atherosclerosis in patients with potential hyperglycemia. Methods A total of 221 patients were recruited among those with potential hype...Objective To investigate the relationship between insulin resistance and carotid atherosclerosis in patients with potential hyperglycemia. Methods A total of 221 patients were recruited among those with potential hyperglycemia. All participants underwent physical examination, medical history interview, and 75 g oral glucose tolerance test. Venous blood was sampled for measurement of insulin and cholesterol levels. The intima-media thickness (IMT) in bilateral common carotid arteries was observed by B-mode ultrasound. Insulin resistance index was calculated by homeostasis model assessment (HOMA-IR). Subjects were stratified in quintiles according to HOMA-IR values. Risk factors and atherosclerotic parameters were analyzed. Results With HOMA-IR value increase, incidence of impaired glucose tolerance, diabetes mellitus, hypertension, and coronary artery disease increased, the levels of triglyceride (TG), low density lipoprotein cholesterol (LDL-C), fasting plasma glucose, 2 hour plasma glucose, and fasting insulin increased as well, while the level of high density lipoprotein cholesterol (HDL-C) decreased. Meanwhile, all atherosclerotic parameters increased. Multivariate regression analysis showed that TG, total cholesterol, HDL-C, LDL-C levels, and ln(HOMA-IR) were related to IMT, hence were risk factors for IMT increase. Conclusion Insulin resistance is implicated in atherogenesis.展开更多
Many studies on oxidative stress,insulin resistance,and antioxidant treatment have shown that increased oxidative stress may accelerate the development of diabetic complications through the excessive glucose and free ...Many studies on oxidative stress,insulin resistance,and antioxidant treatment have shown that increased oxidative stress may accelerate the development of diabetic complications through the excessive glucose and free fatty acids metabolism in diabetic and insulin-resistant states.Many pathogenic mechanisms such as insulin receptor substrate phosphorylation are involved in insulin resistance induced by oxidative stress.And antioxidant treatments can show benefits in animal models of diabetes mellitus and insulin resistance.However,negative evidence from large clinical trials suggests that new and more powerful antioxidants need to be studied to demonstrate whether antioxidants can be effective in treating diabetic complications.Furthermore,it appears that oxidative stress is only one of the factors contributing to diabetic complications.Thus,antioxidant treatment would most likely be more effective if it were coupled with other treatments for diabetic complications.展开更多
Obesity-induced insulin resistance is the hallmark of metabolic syndrome,and chronic,low-grade tissue inflammation links obesity to insulin resistance through the activation of tissue-infiltrating immune cells.Current...Obesity-induced insulin resistance is the hallmark of metabolic syndrome,and chronic,low-grade tissue inflammation links obesity to insulin resistance through the activation of tissue-infiltrating immune cells.Current therapeutic approaches lack efficacy and immunomodulatory capacity.Thus,a new therapeutic approach is needed to prevent chronic inflammation and alleviate insulin resistance.Here,we synthesized a tetrahedral framework nucleic acid(tFNA)nanoparticle that carried resveratrol(RSV)to inhibit tissue inflammation and improve insulin sensitivity in obese mice.The prepared nanoparticles,namely tFNAs-RSV,possessed the characteristics of simple synthesis,stable properties,good water solubility,and superior biocompatibility.The tFNA-based delivery ameliorated the lability of RSV and enhanced its therapeutic efficacy.In high-fat diet(HFD)-fed mice,the administration of tFNAs-RSV ameliorated insulin resistance by alleviating inflammation status.tFNAs-RSV could reverse M1 phenotype macrophages in tissues to M2 phenotype macrophages.As for adaptive immunity,the prepared nanoparticles could repress the activation of Th1 and Th17 and promote Th2 and Treg,leading to the alleviation of insulin resistance.Furthermore,this study is the first to demonstrate that tFNAs,a nucleic acid material,possess immunomodulatory capacity.Collectively,our findings demonstrate that tFNAs-RSV alleviate insulin resistance and ameliorate inflammation in HFD mice,suggesting that nucleic acid materials or nucleic acid-based delivery systems may be a potential agent for the treatment of insulin resistance and obesity-related metabolic diseases.展开更多
Soy consumption has been associated with potential health benefits in reducing chronic diseases.These physiological functions have been attributed to soy proteins or more commonly to bioactive peptides.Thus,more studi...Soy consumption has been associated with potential health benefits in reducing chronic diseases.These physiological functions have been attributed to soy proteins or more commonly to bioactive peptides.Thus,more studies are required to identify these bioactive peptides,and elucidate their biological mechanisms of action.In the present study,a novel peptide iglycin was purifi ed from soybean seeds with a molecular mass of 3.88 k Da.Thereafter,iglycin reduced fasting blood glucose and restored insulin sensitivity of C57 BL/6 J mice on a high-fat diet with increased phosphorylation of insulin receptor substrate 1(IRS1)and AKT in adipose tissue.Furthermore,it improved glucose uptake,induced translocation of intracellular GLUT4 to plasma membrane and activation of insulin signaling in adipocytes under insulin-resistant condition.In addition,it decreased reactive oxygen species production,lipid peroxidation and inhibited adipocyte apoptosis with improved mitochondrial function as evidenced by up-regulation of succinate dehydrogenase activity,mitochondrial membrane potential and intracellular ATP store.These data suggested that iglycin ameliorated insulin resistance via activation of insulin signaling,which was associated with inhibition of oxidative stress,adipocyte apoptosis,and improvement of mitochondrial function.展开更多
Gynostemma pentaphyllum,also called"Southern Ginseng"in China,is a traditional Asian folk medicinal plant.Gypenosides(Gps)are the biologically active constituents of G.pentaphyllum,which have been reported w...Gynostemma pentaphyllum,also called"Southern Ginseng"in China,is a traditional Asian folk medicinal plant.Gypenosides(Gps)are the biologically active constituents of G.pentaphyllum,which have been reported with hypoglycemic activity.However,the underlying mechanisms are unclear.The effects of two Gps(Gp-Ⅰand Gp-Ⅱ)on type 2 diabetic mellitus(T2DM)mice,induced by high-fat and high-sugar diet and streptozotocin,were evaluated to explore the mechanism of their hypoglycemic actions.Gps reduced fasting blood glucose and serum lipids,as well as significantly improved T2DM mice glucose tolerance and insulin resistance(IR).After Gps treatment,the severity of liver injury was reduced and liver glycogen content increased.In addition,Gps promoted the phosphorylation of adenosine monophosphate-activated protein kinase(AMPK),and downregulated the key proteins phosphoenolpyruvate carboxy kinase and glucose-6 phosphatase,in the AMPK signaling pathway.Thus,our study suggests that Gps mediate hepatic gluconeogenesis and improve IR via activating AMPK signaling pathway in T2DM mice.展开更多
Compounds with regulating glucose metabolism and improving insulin resistance(IR)activity are abundant in nature and can be obtained from several sources.They have high potential to be used to treat diabetes mellitus....Compounds with regulating glucose metabolism and improving insulin resistance(IR)activity are abundant in nature and can be obtained from several sources.They have high potential to be used to treat diabetes mellitus.These compounds isolated from natural plants can be classified seven categories:terpenoids,alkaloids,quinones,flavonoids,phenols,phenyl propanoids,steroids,and other types of compounds.They exert biological effects by different ways and mechanisms.This review illustrated the potential natural products as a rich resource in regulation of glucose metabolism and IR,as well as their mechanisms.展开更多
Background Insulin resistance （IR） is present at all stages of chronic kidney disease （CKD） and is associated with CKD progression. Probueol can improve the prognosis of IR in diabetes mellitus （DM） patients. Th...Background Insulin resistance （IR） is present at all stages of chronic kidney disease （CKD） and is associated with CKD progression. Probueol can improve the prognosis of IR in diabetes mellitus （DM） patients. This study aimed to observe the effect of probucol on IR and kidney protection in non-diabetic CKD patients. Methods This was an open-label, non-placebo-controlled, randomized study. A total of 59 patients were randomized to the probucol group （0.5 g, twice daily） or the control group using a 1： 1 treatment ratio. IR was determined using a homeostatic model assessment-IR （HOMA-IR） index. An Excel database was established to analyze foUow-up data at weeks 0, 12, and 24. The primary outcome of interest was changes in the HOMA-IR, and the secondary outcomes of interest were changes in the estimated glomerular filtration rate （eGFR）, body mass index （BMI）, cholesterol, triglycerides, high-density lipoprotein （HDL）, low-density lipoprotein （LDL）, and 24-h urinary protein. Results The HOMA-IR index of the probucol group after 24 weeks was significantly decreased （P 〈 0.001） compared to the value before treatment （average decrease： 1.45; range： -2.90 to -0.43）. The HOMA-IR index in the control group increased （average increase： 0.54; range： -0.38 to 1.87）. For the secondary outcomes of interest, the changes between these two groups also exhibited significant differences in eGFR （P = 0.041）, cholesterol （P = 0.001）, fasting insulin （P 〈 0.001）, and fasting C-peptide （P = 0.001）. Conclusions Compared to angiotensin receptor blockers alone, the combination with probucol ameliorates IR in non-diabetic CKD patients and delays disease progression.展开更多
Insulin resistance(IR) has been considered to be an important causative factor of metabolic syndrome(Met S). The present study investigated whether pomegranate peel polyphenols(PPPs) could prevent the development of M...Insulin resistance(IR) has been considered to be an important causative factor of metabolic syndrome(Met S). The present study investigated whether pomegranate peel polyphenols(PPPs) could prevent the development of Met S by improving IR in rats. Male Sprague-Dawley(SD) rats were fed high fat diet(HFD) to induce Met S and supplemented with different dosages of PPPs for 12 weeks. The results showed that HFD-induced insulin resistant rats had disordered metabolism of blood glucose, blood lipid, and terrible muscle fiber morphology when compared with normal diet-fed rats, but PPPs treatment at a dosage of 300 mg/kg·day significantly reversed these negative effects. Moreover, in skeletal muscle tissue of insulin resistant rats, PPPs treatments significantly increased the protein expressions of insulin receptor(Ins R) and phosphorylated insulin receptor substrate 1(IRS-1), stimulated peroxisome proliferator activated receptor gamma(PPARγ) and phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT/PKB) signaling pathway, and aggrandized the protein levels of phosphorylated glycogen synthase kinase-3β(GSK-3β) and glucose transporter 4(GLUT4). Our results suggest that PPPs possess of the beneficial effects on alleviating IR by enhancing insulin sensitivity and regulating glucose metabolism.展开更多
It is unclear how docosahexaenoic acid(DHA)improves insulin resistance via modulating gut microbiome in obese individuals.We used diet-induced obesity(DIO)mice as a model to study the effects of DHA-rich fish oil(DHA-...It is unclear how docosahexaenoic acid(DHA)improves insulin resistance via modulating gut microbiome in obese individuals.We used diet-induced obesity(DIO)mice as a model to study the effects of DHA-rich fish oil(DHA-FO)on host metabolic disorders and colonic microbiome.DHA-FO reduced fat deposition,regulated lipid profiles and alleviated insulin resistance in DIO mice.Probably because DHA-FO prevented the permeation of lipopolysaccharide across intestinal epithelial barrier,and promoted peptide YY(PYY)secretion via the mediation of short chain fatty acids receptor(FFAR2)in colon.Furthermore,DHA-FO might regulate PYY expression by reversing microbial dysbiosis,including increasing the abundance ofAkkermansia muciniphila and Lactobacillus,and suppressing the growth of Helicobacter.DHA-FO also altered gut microbial function(e.g."linoleic acid metabolism")associated with PYY expression(r>0.80,P<0.05).Herein,DHA-FO enhanced insulin action on glucose metabolism by altering gut microbiome and facilitating colonic PYY expression in DIO mice.展开更多
The benefits of angiotensin converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) beyond blood pressure reduction have been proven through many large studies (HOPE, LIFE) in high risk CVD patie... The benefits of angiotensin converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) beyond blood pressure reduction have been proven through many large studies (HOPE, LIFE) in high risk CVD patients;1 post hoc studies have shown reductions in new onset type 2 diabetes mellitus (DM). ……展开更多
Objective To investigate the potential role of nucleotide-binding oligomerization domain 1 （NOD1）, a component of the innate immune system, in mediating lipid-induced insulin resistance in adipocytes. Methods Adipo...Objective To investigate the potential role of nucleotide-binding oligomerization domain 1 （NOD1）, a component of the innate immune system, in mediating lipid-induced insulin resistance in adipocytes. Methods Adipocytes from Toll-like receptor 4 deficiency mice were used for stimulation experiments. The effect of oleate/palmitate mixture on nuclear factor-κB （NF-κB） activation was analyzed by reporter plasmid assay. The release of proinflammatory chemokine/cytokines production was determined by using real-time PCR. Insulin-stimulated glucose uptake was measured by 2-deoxy-D-[SH] glucose uptake assay. Chemokine/cytokine expression and glucose uptake in adipocytes transfected with small interfering RNA （siRNA） targeting NOD 1 upon fatty acids treatment were analyzed. Results Oleate/palmitate mixture activated the NF-κB pathway and induced interleukin-6, tumor necrosis factor-R, and monocyte chemoattractant protein-1 mRNA expressions in adipocytes from mice deficient in Toll-like receptor 4, and these effects were blocked by siRNA targeting NOD1. Furthermore, saturated fatty acids decreased the ability of insulin-stimulated glucose uptake. Importantly, siRNA targeting NOD 1 partially reversed saturated fatty acid-induced suppression of insulin-induced glucose uptake. Conclusion NOD1 might play an important role in saturated fatty acid-induced insulin resistance in adipocytes, suggesting a mechanism by which reduced NOD1 activity confers beneficial effects on insulin action.展开更多
Obesity-induced type 2 diabetes is mainly due to excessive free fatty acids leading to insulin resistance.Increasing thermogenesis is regarded as an effective strategy for hypolipidemia and hypoglycemia.Ginsenoside is...Obesity-induced type 2 diabetes is mainly due to excessive free fatty acids leading to insulin resistance.Increasing thermogenesis is regarded as an effective strategy for hypolipidemia and hypoglycemia.Ginsenoside is a natural active component in Panax ginseng C.A.Meyer,and some of them enhance thermogenesis.However,there are few studies on the mechanism and target of ginsenosides enhancing thermogenesis.Using thermogenic protein uncoupling protein 1(UCP1)-luciferase reporter assay,we identifi ed ginsenoside F1 as a novel UCP1 activator in the ginsenosides library.Using pull down assay and inhibitor interference,we found F1 binds toβ3-adrenergic receptors(β3-AR)to enhance UCP1 expression via cAMP/PKA/CREB pathway.We also investigated the ability of F1 on energy metabolism in obesity-induced diabetic mice,including body weight,body composition and energy expenditure.The results of proteomics showed that F1 signifi cantly up-regulated thermogenesis proteins and lipolytic proteins,but down-regulated fatty acid synthesis proteins.Ginsenoside F1 increased thermogenesis and ameliorated insulin resistance specifi cally by promoting the browning of white adipose tissue in obese mice.Additionally,ginsenoside F1 improves norepinephrine-induced insulin resistance in adipocytes and hepatocytes,and shows a stronger mitochondria respiration ability than norepinephrine.These fi ndings suggest that ginsenoside F1 is a promising lead compound in the improvement of insulin resistance.展开更多
Insulin resistance leads to impaired glucose metabolism by disrupting both insulin secretion and sensitivity.Insulin resistance plays a key role in the pathophysiology of type 2 diabetes and metabolic syndrome.Reviews...Insulin resistance leads to impaired glucose metabolism by disrupting both insulin secretion and sensitivity.Insulin resistance plays a key role in the pathophysiology of type 2 diabetes and metabolic syndrome.Reviews on the mechanisms of action of bioactive peptides on glucose homeostasis and insulin resistance are scarce.The recent discoveries of pathways and target cells in the management of glucose and energy metabolism have opened up new opportunities for identification of novel bioactive peptides on enhancing adipocyte differentiation and insulin signaling,glucose uptake,cholecystokinin receptor expression and activation,as well as insulin mimetics and incretin stimulants.Examples of food-derived bioactive peptides with glucoregulatory properties include Trp-Glu-Lys-Ala-Phe-Lys-Asp-Glu-Asp(WEKAFKDED),Gln-Ala-MetPro-Phe-Arg-Val-Thr-Glu-Gln-Glu(QAMPFRVTEQE),Glu-Arg-Tyr-Pro-Ile-Leu(ERKPIL),Val-Phe-LysGly-Leu(VFKGL),Phe-Leu-Val(FLV),Val-Pro-Pro(VPP),Ile-Arg-Trp(IRW),Ala-Lys-Ser-Pro-Leu-Phe(AKSPLF),Ala-Thr-Gln-Pro-Leu-Phe(ATNPLF),Phe-Glu-Glu-Leu-Gln(FEELN),Leu-Ser-Val-Ser-Val-Leu(LSVSVL),Val-Arg-Ileu-Arg-Leu-Leu-Gln-Arg-Phe-Asn-Lys-Arg-Ser(VRIRLLQRFNKRS),and Ala-GlyPhe-Ala-Gly-Asp-Asp-Ala-Pro-Arg(AGFAGDDAPR).However,as yet,clinical evidence on the effi cacy of such bioactive peptides is rare but is inevitable to establish their applications against glucose intolerance and insulin resistance.展开更多
Patrinia scabiosaefolia,is used as wild vegetable in China for more than 2000 years,with a variety of pharmacological activities,including anti-inflammatory,anti-tumor and hypoglycemic.Based on our ongoing research on...Patrinia scabiosaefolia,is used as wild vegetable in China for more than 2000 years,with a variety of pharmacological activities,including anti-inflammatory,anti-tumor and hypoglycemic.Based on our ongoing research on chemical constituents and hypoglycemic activity of P.scabiosaefolia,4 lignan compounds,(+)-isolariciresinol(1),7R,7’R,8S,8’S-(+)-neo-olivil-4-O-β-D-glucopyranoside(2),4-O-methylcedrusin(3)and patrinian A(4),were isolated and identifi ed.The hypoglycemic activity showed that compounds 2 and 3 could extremely signifi cantly improve insulin resistance at 100(P<0.001),50(P<0.001)and 25μmol/L(P<0.01)in IR 3T3-L1 cells.While compound 4 only promoted glucose uptake by IR 3T3-L1 cells at 100μmol/L(P<0.01).Western blotting experiments showed that compounds 2 and 4 up-regulated the protein expressions of p-IRS,PI-3K,p-AKT and glucose transporter 4(GLUT4),and promoted the transcription of GLUT4 mRNA.Therefore,the mechanisms of compounds 2 and 4 were presumed to improve IR by activating PI-3K/AKT signaling pathway.展开更多
Objective To investigate the expression of phosphatase and tension homolog(PTEN) in adipose tissue of KKAy diabetic mice, a mouse model of type 2 diabetes. Methods KKAy diabetic mice were fed with high fat diet for 4 ...Objective To investigate the expression of phosphatase and tension homolog(PTEN) in adipose tissue of KKAy diabetic mice, a mouse model of type 2 diabetes. Methods KKAy diabetic mice were fed with high fat diet for 4 weeks. After blood glucose met the criteria of diabetes(over 16.7 mmol/L), mice were randomly divided into 3 groups: a control group(without any treatment), a rosiglitazone group(treated with rosiglitazone 12.5 mg/kg·d once per day), and a metformin group(treated with metformin 3 g/kg·d twice daily). After 4 weeks, we then determined the expression of PTEN and phosphoserine 473-Akt(pS473-Akt) in the epididymal adipose tissue with Western blots. The mice in each group were further divided into the insulin(-) subgroup and insulin(+) subgroup, which were intraperitoneally injected with saline and insulin(5 mU/g body weight), respectively. Results The expression of PTEN was elevated in the epididymal adipose tissue obtained from KKAy diabetic mice compared with that from the C57BL/6J mice(P<0.001). In accordance with the enhanced expression of PTEN, the level of pS473-Akt stimulated by insulin was decreased in the adipose tissue of KKAy mice compared to the C57BL/6J mice(P<0.001). Treatment with the insulin-sensitizing agents, rosiglitazone and metformin did not inhibit the elevated expression of PTEN in adipose tissue of KKAy diabetic mice. Conclusion PTEN may play an important role in the development of insulin resistance in adipose tissue of type 2 diabetes mice model.展开更多
Inflammatory stimulation plays a significant role in the development and worsening of insulin-resistant diabetes.Therefore,it is crucial to identify therapeutic agents that can alleviate insulin resistance by targetin...Inflammatory stimulation plays a significant role in the development and worsening of insulin-resistant diabetes.Therefore,it is crucial to identify therapeutic agents that can alleviate insulin resistance by targeting inflammation.Here,we present evidence that Bakuchiol(BL),a monoterpene phenolic compound first discovered from Psoralea corylifolia L.as traditional Chinese medicine,can effectively improve insulin resistance in diabetic mice through anti-inflammation.Our findings demonstrate that BL alleviates inflammation by inhibiting the toll-like receptor 4/nuclear factorκB/mitogen-activated protein kinase axis,consequently enhancing insulin receptor signaling through the c-Jun N-terminal kinase/suppressors of cytokine signaling 3/insulin receptor substrate1 pathway and improving glucolipid homeostasis.Furthermore,the insulin recovery achieved with BL(60 mg/kg)was comparable to that of metformin(200 mg/kg).These results provide further support for considering BL as a potential treatment option for insulin-resistant diabetes mellitus.展开更多
Objective:To study the changes of true insulin(TI) and immunoreactive insulin (IRI) in subjects with NGT, IGT and DM, to study the difference between true insulin and immunoreactive insulin in evaluating βcell functi...Objective:To study the changes of true insulin(TI) and immunoreactive insulin (IRI) in subjects with NGT, IGT and DM, to study the difference between true insulin and immunoreactive insulin in evaluating βcell function and insulin sensitivity. Methods:The levels of serum IRI and TI were determined in 54 cases with type Ⅱ diabetes mellitus(Group DM) ,43 cases with impaired glucose tolerance (Group IGT) and 75 cases with normal glucose tolerance (Group NGT). Then every group was subdivided into obese and non - obese subgroups according to body mass index. IRI was determined by RIA. TI was determined by ELISA using monoclonal antibody with no significant cross- reaction between insulin and proinsulin. The insulin resistance index (Homa- IR), pancreatic β- cell function index (Homa- B) and insulin release index (the ratio of the increment of insulin to that of plasma glucose 30 min after a glucose load,△ I30/△G30) were analyzed preliminarily. Results: The ratio of TI/IRI in non - obese subgroup with DM was lower than those in non obese subgroups with NGT and IGT (P＜0.01). The ratios of TI/Ipd in obese subgroups with IGT and DM were lower than those in obese subgroup with NGT(P＜0.05). The pancreatic β-cell function indexes (Homa-BIRI) of IRI in non- obese subgroups with IGT and DM were lower than that in non- obese subgroup with NGT(P＜0.05). The pancreatic β - cell function index (Homa- BTI) of TI in non- obese subgroup with IGT was lower than that in non obese subgroups with NGT ( P ＜ 0.05 ). The HomaBTI in non - obese subgroup with DM was lower than that in non - obese subgroups with NGT and IGT(P ＜0.01).The Homa - BIRI in obese subgroups of NGT, IGT and DM had no significant difference. Homa - BTI in obese subgroups with IGT and DM was lower than that in obese subgroup with NGT(P＜0.01). Conclusion:The ratio of TI/IRI was a good marker in evaluating β- cell function. Pancreatic β- cell function index (Homa- BTI) of TI was better than that of IRI.展开更多
基金supported by the “Thirteenth Five Year” National Science and Technology Plan Project of China (2018YFC1603703,2018YFC1604302)National Natural Science Foundation of China (2013BAD18B03)+1 种基金Shenyang Technological Innovation Project (Y170-028)LiaoNing Revitalization Talents Project (XLYC1902083)
文摘This study investigated the effects of a xylitol-casein non-covalent complex(XC)on parameters related to type 2 diabetes mellitus(T2DM),in addition to related changes in gut microbiome composition and functions.High-fat-diet(HFD)+streptozotocin(STZ)-induced T2DM mice were treated with xylitol(XY),casein(CN),and XC,after which fecal samples were collected for gut microbiota composition and diversity analyses based on 16S rRNA high-throughput sequencing and multivariate statistics.XC decreased body weight and improved glucose tolerance,insulin sensitivity,pancreas impairment,blood lipid levels,and liver function in T2DM mice compared to XY-and CN-treated mice.Furthermore,XC modulated theα-diversity,β-diversity and gut microbiota composition.Based on Spearman’s correlation analysis,the relative abundances of Alistipes,Bacteroides,and Faecalibaculum were positively correlated and those of Akkermansia,Lactobacillus,Bifidobacterium,and Turicibacter were negatively correlated with the phenotypes related to the improvement of T2DM.In conclusion,we found that XC alleviated insulin resistance by restoring the gut microbiota of T2DM mice.Our results provide strong evidence for the beneficial effects of XC on T2DM and motivation for further investigation in animal models and,eventually,human trials.
基金by National Natural Science Foundation of China(81803224)Young Scholars Program of Shandong University(2018WLJH33)to X.G.+3 种基金National Natural Science Foundation of China(81973031)Cheeloo Young Scholar Program of Shandong University(21320089963054)to H.W.Young Scholars Program of Shandong University(2018WLJH34)the Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology(LMDBKF-2019-05)to L.D.
文摘With the prevalence of obesity and obesity-related metabolic syndrome,such as insulin resistance in recent years,it is urgent to explore effective interventions to prevent the progression of obesity-related metabolic syndrome.Palmitoleic acid is a monounsaturated fatty acid that is available from dietary sources,mainly derived from marine products.P almitoleic acid plays a positive role in maintaining glucose homeostasis and reducing inflammation.However,it is still unknow the mechanism of palmitoleic acid in ameliorating insulin resistance.Here,we investigated the effects of palmitoleic acid on chow diet(CD)-fed and high-fat diet(HFD)-fed mice,which were fed CD or HFD for 12 weeks before administration.We administrated mice with BSA(control),oleic acid,or palmitoleic acid for 6 weeks on top of CD or HFD feeding.We found that palmitoleic acid only improved glucose homeostasis in HFD-fed obese mice by increasing glucose clearance and reducing HOMA-IR.Further study explored that palmitoleic acid changed the composition of gut microbiota by decreasing Firmicutes population and increasing Bacteroidetes population.In colon,palmitoleic acid increased intestinal tight junction integrity and reduced inflammation.Moreover,palmitoleic acid decreased macrophage infiltration in liver and adipose tissue and increase glucose uptake in adipose tissue.Diacylglycerol(DAG)in tissue(for example,liver)is found to positively correlated with HOMA-IR.HFD enhanced the levels of DAGs in liver but not in adipose tissue in this study.Palmitoleic acid did not reverse the high DAG levels induced by HFD in liver.Therefore,in HFD-fed mice,palmitoleic acid reduced insulin resistance by an independent-manner of DAGs.It might be associated with the beneficial effects of palmitoleic acid on altering the gut microbiota composition,improving of intestinal barrier function,and downregulating the inflammation in colon,liver,and adipose tissue.
文摘Objective To investigate the relationship between insulin resistance and carotid atherosclerosis in patients with potential hyperglycemia. Methods A total of 221 patients were recruited among those with potential hyperglycemia. All participants underwent physical examination, medical history interview, and 75 g oral glucose tolerance test. Venous blood was sampled for measurement of insulin and cholesterol levels. The intima-media thickness (IMT) in bilateral common carotid arteries was observed by B-mode ultrasound. Insulin resistance index was calculated by homeostasis model assessment (HOMA-IR). Subjects were stratified in quintiles according to HOMA-IR values. Risk factors and atherosclerotic parameters were analyzed. Results With HOMA-IR value increase, incidence of impaired glucose tolerance, diabetes mellitus, hypertension, and coronary artery disease increased, the levels of triglyceride (TG), low density lipoprotein cholesterol (LDL-C), fasting plasma glucose, 2 hour plasma glucose, and fasting insulin increased as well, while the level of high density lipoprotein cholesterol (HDL-C) decreased. Meanwhile, all atherosclerotic parameters increased. Multivariate regression analysis showed that TG, total cholesterol, HDL-C, LDL-C levels, and ln(HOMA-IR) were related to IMT, hence were risk factors for IMT increase. Conclusion Insulin resistance is implicated in atherogenesis.
基金Supported by grant from the National Basic Research Program (973Program) (2006CB503903)
文摘Many studies on oxidative stress,insulin resistance,and antioxidant treatment have shown that increased oxidative stress may accelerate the development of diabetic complications through the excessive glucose and free fatty acids metabolism in diabetic and insulin-resistant states.Many pathogenic mechanisms such as insulin receptor substrate phosphorylation are involved in insulin resistance induced by oxidative stress.And antioxidant treatments can show benefits in animal models of diabetes mellitus and insulin resistance.However,negative evidence from large clinical trials suggests that new and more powerful antioxidants need to be studied to demonstrate whether antioxidants can be effective in treating diabetic complications.Furthermore,it appears that oxidative stress is only one of the factors contributing to diabetic complications.Thus,antioxidant treatment would most likely be more effective if it were coupled with other treatments for diabetic complications.
基金National Key R&D Program of China(2019YFA0110600)National Natural Science Foundation of China(81970916,81671031)the LU JIAXI International team program supported by the K.C.Wong Education Foundation and CAS and the Youth Innovation Promotion Association of CAS(Grant No.2016236).
文摘Obesity-induced insulin resistance is the hallmark of metabolic syndrome,and chronic,low-grade tissue inflammation links obesity to insulin resistance through the activation of tissue-infiltrating immune cells.Current therapeutic approaches lack efficacy and immunomodulatory capacity.Thus,a new therapeutic approach is needed to prevent chronic inflammation and alleviate insulin resistance.Here,we synthesized a tetrahedral framework nucleic acid(tFNA)nanoparticle that carried resveratrol(RSV)to inhibit tissue inflammation and improve insulin sensitivity in obese mice.The prepared nanoparticles,namely tFNAs-RSV,possessed the characteristics of simple synthesis,stable properties,good water solubility,and superior biocompatibility.The tFNA-based delivery ameliorated the lability of RSV and enhanced its therapeutic efficacy.In high-fat diet(HFD)-fed mice,the administration of tFNAs-RSV ameliorated insulin resistance by alleviating inflammation status.tFNAs-RSV could reverse M1 phenotype macrophages in tissues to M2 phenotype macrophages.As for adaptive immunity,the prepared nanoparticles could repress the activation of Th1 and Th17 and promote Th2 and Treg,leading to the alleviation of insulin resistance.Furthermore,this study is the first to demonstrate that tFNAs,a nucleic acid material,possess immunomodulatory capacity.Collectively,our findings demonstrate that tFNAs-RSV alleviate insulin resistance and ameliorate inflammation in HFD mice,suggesting that nucleic acid materials or nucleic acid-based delivery systems may be a potential agent for the treatment of insulin resistance and obesity-related metabolic diseases.
基金jointly supported by the National Natural Science Foundation of China(31400794)Sichuan Province Science Fund s for Distinguished Young Scholar(2019JDJQ0017)+1 种基金Young and middle-aged Talents Project of the National People’s Commission(2799300127)Fundamental Research Funds for the Central Universities,Southwest Minzu University(2019XMJXPY08)。
文摘Soy consumption has been associated with potential health benefits in reducing chronic diseases.These physiological functions have been attributed to soy proteins or more commonly to bioactive peptides.Thus,more studies are required to identify these bioactive peptides,and elucidate their biological mechanisms of action.In the present study,a novel peptide iglycin was purifi ed from soybean seeds with a molecular mass of 3.88 k Da.Thereafter,iglycin reduced fasting blood glucose and restored insulin sensitivity of C57 BL/6 J mice on a high-fat diet with increased phosphorylation of insulin receptor substrate 1(IRS1)and AKT in adipose tissue.Furthermore,it improved glucose uptake,induced translocation of intracellular GLUT4 to plasma membrane and activation of insulin signaling in adipocytes under insulin-resistant condition.In addition,it decreased reactive oxygen species production,lipid peroxidation and inhibited adipocyte apoptosis with improved mitochondrial function as evidenced by up-regulation of succinate dehydrogenase activity,mitochondrial membrane potential and intracellular ATP store.These data suggested that iglycin ameliorated insulin resistance via activation of insulin signaling,which was associated with inhibition of oxidative stress,adipocyte apoptosis,and improvement of mitochondrial function.
基金supported by the National Natural Science Foundation of China(81602983)。
文摘Gynostemma pentaphyllum,also called"Southern Ginseng"in China,is a traditional Asian folk medicinal plant.Gypenosides(Gps)are the biologically active constituents of G.pentaphyllum,which have been reported with hypoglycemic activity.However,the underlying mechanisms are unclear.The effects of two Gps(Gp-Ⅰand Gp-Ⅱ)on type 2 diabetic mellitus(T2DM)mice,induced by high-fat and high-sugar diet and streptozotocin,were evaluated to explore the mechanism of their hypoglycemic actions.Gps reduced fasting blood glucose and serum lipids,as well as significantly improved T2DM mice glucose tolerance and insulin resistance(IR).After Gps treatment,the severity of liver injury was reduced and liver glycogen content increased.In addition,Gps promoted the phosphorylation of adenosine monophosphate-activated protein kinase(AMPK),and downregulated the key proteins phosphoenolpyruvate carboxy kinase and glucose-6 phosphatase,in the AMPK signaling pathway.Thus,our study suggests that Gps mediate hepatic gluconeogenesis and improve IR via activating AMPK signaling pathway in T2DM mice.
基金supported by National Natural Science Foundation of China(31900292)Science and Technology Development Program of Henan Province(202102110149,192102110112,and 182102410083)Science and Technology Project of Kaifeng(1908005,and 1803010).
文摘Compounds with regulating glucose metabolism and improving insulin resistance(IR)activity are abundant in nature and can be obtained from several sources.They have high potential to be used to treat diabetes mellitus.These compounds isolated from natural plants can be classified seven categories:terpenoids,alkaloids,quinones,flavonoids,phenols,phenyl propanoids,steroids,and other types of compounds.They exert biological effects by different ways and mechanisms.This review illustrated the potential natural products as a rich resource in regulation of glucose metabolism and IR,as well as their mechanisms.
文摘Background Insulin resistance （IR） is present at all stages of chronic kidney disease （CKD） and is associated with CKD progression. Probueol can improve the prognosis of IR in diabetes mellitus （DM） patients. This study aimed to observe the effect of probucol on IR and kidney protection in non-diabetic CKD patients. Methods This was an open-label, non-placebo-controlled, randomized study. A total of 59 patients were randomized to the probucol group （0.5 g, twice daily） or the control group using a 1： 1 treatment ratio. IR was determined using a homeostatic model assessment-IR （HOMA-IR） index. An Excel database was established to analyze foUow-up data at weeks 0, 12, and 24. The primary outcome of interest was changes in the HOMA-IR, and the secondary outcomes of interest were changes in the estimated glomerular filtration rate （eGFR）, body mass index （BMI）, cholesterol, triglycerides, high-density lipoprotein （HDL）, low-density lipoprotein （LDL）, and 24-h urinary protein. Results The HOMA-IR index of the probucol group after 24 weeks was significantly decreased （P 〈 0.001） compared to the value before treatment （average decrease： 1.45; range： -2.90 to -0.43）. The HOMA-IR index in the control group increased （average increase： 0.54; range： -0.38 to 1.87）. For the secondary outcomes of interest, the changes between these two groups also exhibited significant differences in eGFR （P = 0.041）, cholesterol （P = 0.001）, fasting insulin （P 〈 0.001）, and fasting C-peptide （P = 0.001）. Conclusions Compared to angiotensin receptor blockers alone, the combination with probucol ameliorates IR in non-diabetic CKD patients and delays disease progression.
基金supported by the National Natural Science Foundation of China (31871801, 32001679)the Science and Technology Research of Shaanxi Province (2020QFY08-03)+1 种基金Forestry Science and Technology Programs of Shaanxi Province (SXLK20200213)Fundamental Research Funds for the Central Universities (GK201604013)。
文摘Insulin resistance(IR) has been considered to be an important causative factor of metabolic syndrome(Met S). The present study investigated whether pomegranate peel polyphenols(PPPs) could prevent the development of Met S by improving IR in rats. Male Sprague-Dawley(SD) rats were fed high fat diet(HFD) to induce Met S and supplemented with different dosages of PPPs for 12 weeks. The results showed that HFD-induced insulin resistant rats had disordered metabolism of blood glucose, blood lipid, and terrible muscle fiber morphology when compared with normal diet-fed rats, but PPPs treatment at a dosage of 300 mg/kg·day significantly reversed these negative effects. Moreover, in skeletal muscle tissue of insulin resistant rats, PPPs treatments significantly increased the protein expressions of insulin receptor(Ins R) and phosphorylated insulin receptor substrate 1(IRS-1), stimulated peroxisome proliferator activated receptor gamma(PPARγ) and phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT/PKB) signaling pathway, and aggrandized the protein levels of phosphorylated glycogen synthase kinase-3β(GSK-3β) and glucose transporter 4(GLUT4). Our results suggest that PPPs possess of the beneficial effects on alleviating IR by enhancing insulin sensitivity and regulating glucose metabolism.
基金funded by National Key R&D Program of China(grant number 2018YFC0311201)China Postdoctoral Science Foundation(No.2020M672147).
文摘It is unclear how docosahexaenoic acid(DHA)improves insulin resistance via modulating gut microbiome in obese individuals.We used diet-induced obesity(DIO)mice as a model to study the effects of DHA-rich fish oil(DHA-FO)on host metabolic disorders and colonic microbiome.DHA-FO reduced fat deposition,regulated lipid profiles and alleviated insulin resistance in DIO mice.Probably because DHA-FO prevented the permeation of lipopolysaccharide across intestinal epithelial barrier,and promoted peptide YY(PYY)secretion via the mediation of short chain fatty acids receptor(FFAR2)in colon.Furthermore,DHA-FO might regulate PYY expression by reversing microbial dysbiosis,including increasing the abundance ofAkkermansia muciniphila and Lactobacillus,and suppressing the growth of Helicobacter.DHA-FO also altered gut microbial function(e.g."linoleic acid metabolism")associated with PYY expression(r>0.80,P<0.05).Herein,DHA-FO enhanced insulin action on glucose metabolism by altering gut microbiome and facilitating colonic PYY expression in DIO mice.
文摘 The benefits of angiotensin converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) beyond blood pressure reduction have been proven through many large studies (HOPE, LIFE) in high risk CVD patients;1 post hoc studies have shown reductions in new onset type 2 diabetes mellitus (DM). ……
基金Supported by the Grant from the Educational Department of Liaoning Province(2008810)
文摘Objective To investigate the potential role of nucleotide-binding oligomerization domain 1 （NOD1）, a component of the innate immune system, in mediating lipid-induced insulin resistance in adipocytes. Methods Adipocytes from Toll-like receptor 4 deficiency mice were used for stimulation experiments. The effect of oleate/palmitate mixture on nuclear factor-κB （NF-κB） activation was analyzed by reporter plasmid assay. The release of proinflammatory chemokine/cytokines production was determined by using real-time PCR. Insulin-stimulated glucose uptake was measured by 2-deoxy-D-[SH] glucose uptake assay. Chemokine/cytokine expression and glucose uptake in adipocytes transfected with small interfering RNA （siRNA） targeting NOD 1 upon fatty acids treatment were analyzed. Results Oleate/palmitate mixture activated the NF-κB pathway and induced interleukin-6, tumor necrosis factor-R, and monocyte chemoattractant protein-1 mRNA expressions in adipocytes from mice deficient in Toll-like receptor 4, and these effects were blocked by siRNA targeting NOD1. Furthermore, saturated fatty acids decreased the ability of insulin-stimulated glucose uptake. Importantly, siRNA targeting NOD 1 partially reversed saturated fatty acid-induced suppression of insulin-induced glucose uptake. Conclusion NOD1 might play an important role in saturated fatty acid-induced insulin resistance in adipocytes, suggesting a mechanism by which reduced NOD1 activity confers beneficial effects on insulin action.
基金supported by the National Natural Science Foundation of China[31872674]the Jilin Talent Development Foundation Grant[20200301018RQ]the Fundamental Research Funds for the Central Universities[CGZH202206].
文摘Obesity-induced type 2 diabetes is mainly due to excessive free fatty acids leading to insulin resistance.Increasing thermogenesis is regarded as an effective strategy for hypolipidemia and hypoglycemia.Ginsenoside is a natural active component in Panax ginseng C.A.Meyer,and some of them enhance thermogenesis.However,there are few studies on the mechanism and target of ginsenosides enhancing thermogenesis.Using thermogenic protein uncoupling protein 1(UCP1)-luciferase reporter assay,we identifi ed ginsenoside F1 as a novel UCP1 activator in the ginsenosides library.Using pull down assay and inhibitor interference,we found F1 binds toβ3-adrenergic receptors(β3-AR)to enhance UCP1 expression via cAMP/PKA/CREB pathway.We also investigated the ability of F1 on energy metabolism in obesity-induced diabetic mice,including body weight,body composition and energy expenditure.The results of proteomics showed that F1 signifi cantly up-regulated thermogenesis proteins and lipolytic proteins,but down-regulated fatty acid synthesis proteins.Ginsenoside F1 increased thermogenesis and ameliorated insulin resistance specifi cally by promoting the browning of white adipose tissue in obese mice.Additionally,ginsenoside F1 improves norepinephrine-induced insulin resistance in adipocytes and hepatocytes,and shows a stronger mitochondria respiration ability than norepinephrine.These fi ndings suggest that ginsenoside F1 is a promising lead compound in the improvement of insulin resistance.
基金supported by Grants from Natural Sciences and Engineering Research Council(NSERC)of CanadaAlberta Agriculture and Forestry,and Egg Farmers of Canada。
文摘Insulin resistance leads to impaired glucose metabolism by disrupting both insulin secretion and sensitivity.Insulin resistance plays a key role in the pathophysiology of type 2 diabetes and metabolic syndrome.Reviews on the mechanisms of action of bioactive peptides on glucose homeostasis and insulin resistance are scarce.The recent discoveries of pathways and target cells in the management of glucose and energy metabolism have opened up new opportunities for identification of novel bioactive peptides on enhancing adipocyte differentiation and insulin signaling,glucose uptake,cholecystokinin receptor expression and activation,as well as insulin mimetics and incretin stimulants.Examples of food-derived bioactive peptides with glucoregulatory properties include Trp-Glu-Lys-Ala-Phe-Lys-Asp-Glu-Asp(WEKAFKDED),Gln-Ala-MetPro-Phe-Arg-Val-Thr-Glu-Gln-Glu(QAMPFRVTEQE),Glu-Arg-Tyr-Pro-Ile-Leu(ERKPIL),Val-Phe-LysGly-Leu(VFKGL),Phe-Leu-Val(FLV),Val-Pro-Pro(VPP),Ile-Arg-Trp(IRW),Ala-Lys-Ser-Pro-Leu-Phe(AKSPLF),Ala-Thr-Gln-Pro-Leu-Phe(ATNPLF),Phe-Glu-Glu-Leu-Gln(FEELN),Leu-Ser-Val-Ser-Val-Leu(LSVSVL),Val-Arg-Ileu-Arg-Leu-Leu-Gln-Arg-Phe-Asn-Lys-Arg-Ser(VRIRLLQRFNKRS),and Ala-GlyPhe-Ala-Gly-Asp-Asp-Ala-Pro-Arg(AGFAGDDAPR).However,as yet,clinical evidence on the effi cacy of such bioactive peptides is rare but is inevitable to establish their applications against glucose intolerance and insulin resistance.
基金funded by National Key R&D Program of China(2022YFF1100300)National Natural Science Foundation of China(31900292)+1 种基金Science and Technology Development Program of Henan Province(212102110469,222102520035)Research on Precision Nutrition and Health Food,Department of Science and Technology of Henan Province(CXJD2021006).
文摘Patrinia scabiosaefolia,is used as wild vegetable in China for more than 2000 years,with a variety of pharmacological activities,including anti-inflammatory,anti-tumor and hypoglycemic.Based on our ongoing research on chemical constituents and hypoglycemic activity of P.scabiosaefolia,4 lignan compounds,(+)-isolariciresinol(1),7R,7’R,8S,8’S-(+)-neo-olivil-4-O-β-D-glucopyranoside(2),4-O-methylcedrusin(3)and patrinian A(4),were isolated and identifi ed.The hypoglycemic activity showed that compounds 2 and 3 could extremely signifi cantly improve insulin resistance at 100(P<0.001),50(P<0.001)and 25μmol/L(P<0.01)in IR 3T3-L1 cells.While compound 4 only promoted glucose uptake by IR 3T3-L1 cells at 100μmol/L(P<0.01).Western blotting experiments showed that compounds 2 and 4 up-regulated the protein expressions of p-IRS,PI-3K,p-AKT and glucose transporter 4(GLUT4),and promoted the transcription of GLUT4 mRNA.Therefore,the mechanisms of compounds 2 and 4 were presumed to improve IR by activating PI-3K/AKT signaling pathway.
基金Supported by National Natural Science Foundation of China(81270878)National Key Program of Clinical Science of China(WBYZ2011-873)
文摘Objective To investigate the expression of phosphatase and tension homolog(PTEN) in adipose tissue of KKAy diabetic mice, a mouse model of type 2 diabetes. Methods KKAy diabetic mice were fed with high fat diet for 4 weeks. After blood glucose met the criteria of diabetes(over 16.7 mmol/L), mice were randomly divided into 3 groups: a control group(without any treatment), a rosiglitazone group(treated with rosiglitazone 12.5 mg/kg·d once per day), and a metformin group(treated with metformin 3 g/kg·d twice daily). After 4 weeks, we then determined the expression of PTEN and phosphoserine 473-Akt(pS473-Akt) in the epididymal adipose tissue with Western blots. The mice in each group were further divided into the insulin(-) subgroup and insulin(+) subgroup, which were intraperitoneally injected with saline and insulin(5 mU/g body weight), respectively. Results The expression of PTEN was elevated in the epididymal adipose tissue obtained from KKAy diabetic mice compared with that from the C57BL/6J mice(P<0.001). In accordance with the enhanced expression of PTEN, the level of pS473-Akt stimulated by insulin was decreased in the adipose tissue of KKAy mice compared to the C57BL/6J mice(P<0.001). Treatment with the insulin-sensitizing agents, rosiglitazone and metformin did not inhibit the elevated expression of PTEN in adipose tissue of KKAy diabetic mice. Conclusion PTEN may play an important role in the development of insulin resistance in adipose tissue of type 2 diabetes mice model.
基金supported by National Key R&D Program of China(2022YFF1100300)the Central Guidance on Local Science and Technology Development Found of Shenzhen,China(2021Szvup030).
文摘Inflammatory stimulation plays a significant role in the development and worsening of insulin-resistant diabetes.Therefore,it is crucial to identify therapeutic agents that can alleviate insulin resistance by targeting inflammation.Here,we present evidence that Bakuchiol(BL),a monoterpene phenolic compound first discovered from Psoralea corylifolia L.as traditional Chinese medicine,can effectively improve insulin resistance in diabetic mice through anti-inflammation.Our findings demonstrate that BL alleviates inflammation by inhibiting the toll-like receptor 4/nuclear factorκB/mitogen-activated protein kinase axis,consequently enhancing insulin receptor signaling through the c-Jun N-terminal kinase/suppressors of cytokine signaling 3/insulin receptor substrate1 pathway and improving glucolipid homeostasis.Furthermore,the insulin recovery achieved with BL(60 mg/kg)was comparable to that of metformin(200 mg/kg).These results provide further support for considering BL as a potential treatment option for insulin-resistant diabetes mellitus.
文摘Objective:To study the changes of true insulin(TI) and immunoreactive insulin (IRI) in subjects with NGT, IGT and DM, to study the difference between true insulin and immunoreactive insulin in evaluating βcell function and insulin sensitivity. Methods:The levels of serum IRI and TI were determined in 54 cases with type Ⅱ diabetes mellitus(Group DM) ,43 cases with impaired glucose tolerance (Group IGT) and 75 cases with normal glucose tolerance (Group NGT). Then every group was subdivided into obese and non - obese subgroups according to body mass index. IRI was determined by RIA. TI was determined by ELISA using monoclonal antibody with no significant cross- reaction between insulin and proinsulin. The insulin resistance index (Homa- IR), pancreatic β- cell function index (Homa- B) and insulin release index (the ratio of the increment of insulin to that of plasma glucose 30 min after a glucose load,△ I30/△G30) were analyzed preliminarily. Results: The ratio of TI/IRI in non - obese subgroup with DM was lower than those in non obese subgroups with NGT and IGT (P＜0.01). The ratios of TI/Ipd in obese subgroups with IGT and DM were lower than those in obese subgroup with NGT(P＜0.05). The pancreatic β-cell function indexes (Homa-BIRI) of IRI in non- obese subgroups with IGT and DM were lower than that in non- obese subgroup with NGT(P＜0.05). The pancreatic β - cell function index (Homa- BTI) of TI in non- obese subgroup with IGT was lower than that in non obese subgroups with NGT ( P ＜ 0.05 ). The HomaBTI in non - obese subgroup with DM was lower than that in non - obese subgroups with NGT and IGT(P ＜0.01).The Homa - BIRI in obese subgroups of NGT, IGT and DM had no significant difference. Homa - BTI in obese subgroups with IGT and DM was lower than that in obese subgroup with NGT(P＜0.01). Conclusion:The ratio of TI/IRI was a good marker in evaluating β- cell function. Pancreatic β- cell function index (Homa- BTI) of TI was better than that of IRI.
