Résumé
Objective To observe the effect of human umbilical cord-derived mesenchymal stem cells (hMSCs) on type 2 diabetic rats, and to explore the possible mechanism. Methods Type 2 diabetic rats were induced by high-fat diet combined with a low dosage of streptozotocin ( STZ, 25 mg/ kg). After 3 × 106 hMSCs suspended in 1 ml PBS or 1ml 10-fold concentrated hMSC supernatant were intravenously infused into the rats via the tail vein, the blood glucose levels were measured every day. One week later, intraperitoneal glucose tolerance test and insulin tolerance test were performed to evaluate the effects of hMSCs on diabetic rats. Pancreatic tissues were collected for insulin/ glucagon immunofluorescence staining. Results After hMSCs infusion, blood glucose level and homeostasis model of assessment for insulin resistance index were significantly decreased in type 2 diabetic rats(both P<0. 01). The glucose tolerance and insulin tolerance were greatly alleviated by hMSCs(all P<0. 01). Intravenously infused 1ml 10-fold concentrated hMSC supernatant showed a similar result to hMSCs. Conclusion In type 2 diabetic rats, hMSCs are able to effectively lower the blood glucose level, improve insulin sensitivity, and increase the number of β cells, which seems to be mediated by their secreted molecules.
Résumé
Objective To study the effect of conditioned media for rat bone marrow mesenchymal stem cells (BMSCs-CM) on palmitic acid (PA)-induced insulin resistance (IR) in HepG2 cells and its underlying molecular mechanisms.Methods HepG2 cells were treated with or without BMSCs-CM and L-DMEM in the presence or absence of PA.Glucose utilization in HepG2 cells were detected with PAS,glucose and glycogen measurements.Western blotting was used to assess the expression of phospho-insulin receptor substrate (p-IRS),phosphatidylinositol 3-kinase (PI3 K) and p-AKT.Results (1) Incubation of HepG2 cells with 0.25 mmol/L PA for 24 hours significantly increased the glucose concentration and decreased the glycogen content (P ＜ 0.05) in the media.(2) Treatment with BMSCs-CM significantly ameliorated the glucose and glycogen alteration in cells pretreated with PA (P ＜ 0.05),however,no obvious effect of BMSCs-CM on the cell glucose and glycogen production.(3) BMSCs-CM treatment also increased protein expression of p-IRS,PI3K and p-AKT in PA incubated HapG2 cells (P＜ 0.05).The effect of BMSCs-CM on PI3K and p-AKT expression could be mimicked upon addition of 740Y-P,a PI3K agonist,but abolished by LY294002,a PI3K specific inhibitor.Conclusions BMSCs-CM could improve the insulin sensitivity in HepG2 cells pretreated with PA through upregulation of insulin signaling component expression.