Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Enhance Insulin Sensitivity in Insulin Resistant Human Adipocytes

Insulin resistance is an essential characteristic of type 2 diabetes mellitus(T2DM),which can be induced by glucotoxicity and adipose chronic inflammation.Mesenchymal stem cells(MSCs)and their exosomes were reported to ameliorate T2DM and its complications by their immunoregulatory and healing abilities.Exosomes derived from MSCs contain abundant molecules to mediate crosstalk between cells and mimic biological function of MSCs.But the role of exosomes derived from human umbilical cord mesenchymal stem cells(hUC-MSCs)in insulin resistance of human adipocytes is unclear.In this study,exosomes were harvested from the conditioned medium of hUC-MSCs and added to insulin-resistant adipocytes.Insulin-stimulated glucose uptake was measured by glucose oxidase/peroxidase assay.The signal pathway involved in exosome-treated adipocytes was detected by RT-PCR and Western blotting.The biological characteristics and function were compared between hUC-MSCs and human adipose-derived mesenchymal stem cells(hAMSCs).The results showed that hAMSCs had better adipogenic ability than hUC-MSCs.After induction of mature adipocytes by adipogenesis of hAMSC,the model of insulin-resistant adipocytes was successfully established by TNF-αand high glucose intervention.After exosome treatment,the insulin-stimulated glucose uptake was significantly increased.In addition,the effect of exosomes could be stabilized for at least 48 h.Furthermore,the level of leptin was significantly decreased,and the mRNA expression of sirtuin-1 and insulin receptor substrate-1 was significantly upregulated after exosome treatment.In conclusion,exosomes significantly improve insulin sensitivity in insulin-resistant human adipocytes,and the mechanism involves the regulation of adipokines.

Early-life nutrition and metabolic disorders in later life:a new perspective on energy metabolism

Type 2 diabetes mellitus and metabolic disorders have become an epidemic globally.However,the pathogenesis remains largely unclear and the prevention and treatment are still limited.In addition to environmental factors during adulthood,early life is the critical developmental window with high tissue plasticity,which might be modified by external environmental cues.Substantial evidence has demonstrated the vital role of early-life nutrition in programming the metabolic disorders in later life.In this review,we aim to overview the concepts of fetal programming and investigate the effects of early-life nutrition on energy metabolism in later life and the potential epigenetic mechanism.The related studies published on PubMed database up to March 2020 were included.The results showed that both maternal overnutrition and undernutrition increased the riskes of metabolic disorders in offspring and epigenetic modifications,including DNA methylation,miRNAs,and histone modification,might be the vital mediators.The beneficial effects of early-life lifestyle modifications as well as dietary and nutritional interventions on these deleterious metabolic remolding were initially observed.Overall,characterizing the early-life malnutrition that reshapes metabolic disease trajectories may yield novel targets for early prevention and intervention and provide a new point of view to the energy metabolism.

Maternal exercise and its beneficial effects on glucose metabolism in offspring

It shows that detrimental exposures and conditions in mothers can lead to the development of obesity and type 2 diabetes in offspring.This can lead to a vicious cycle of metabolic dysfunction,where rising rates of obesity,pre-diabetes,and diabetes in individuals of reproductive age,propagating risks to subsequent generations.It is well established that regular exercise has important health benefits for people with obesity and type 2 diabetes.Recently,increasing studies aim to examine the effects of maternal exercise on metabolic health in offspring.This review aims to demonstrate the evidence linking maternal exercise during critical periods of development and its implications for glucose metabolism in offspring,including intervention timing,sexual dimorphism,different exercise type,and intensity.Then we further examine the potential role of epigenetic modifications in this process.

Potential contribution of the gut microbiota to hypoglycemia after gastric bypass surgery

Obesity has become a global health problem. Lifestyle modification and medical treatment only appear to yield short-term weight loss. Roux-en-Y gastric bypass (RYGB) is the most popular bariatric procedure, and it sustains weight reduction and results in the remission of obesity-associated comorbidities for obese individuals. However, patients who undergo this surgery may develop hypoglycemia. To date, the diagnosis is challenging and the prevalence of post-RYGB hypoglycemia (PRH) is unclear. RYGB alters the anatomy of the upper gastrointestinal tract and has a combined effect of caloric intake restriction and nutrient malabsorption. Nevertheless, the physiologic changes after RYGB are complex. Although hyperinsulinemia, incretin effects, dysfunction of β-cells and α-cells, and some other factors have been widely investigated and are reported to be possible mediators of PRH, the pathogenesis is still not completely understood. In light of the important role of the gut microbiome in metabolism, we hypothesized that the gut microbiome might also be a critical link between RYGB and hypoglycemia. In this review, we mainly highlight the current possible factors predisposing individuals to PRH, particularly related to the gut microbiota, which may yield significant insights into the intestinal regulation of glucose metabolic homeostasis and provide novel clues to improve the treatment of type 2 diabetes mellitus.