Infusion of bone marrow mesenchymal stem cells alleviates insulin resistance and initiates pancreatic regeneration in experimental type 2 diabetic-rats

Abstract

Insulin resistance and defect in insulin-producing pancreatic beta cells are the key features of type 2 diabetes (T2DM). Mesenchymal stem cells isolated from bone marrow (BM-MSCs) have differentiation, anti-inflammatory and immunosuppressive characteristics, making them suitable for treating T2DM. Therefore, the present study aimed at investigating the possible therapeutic mechanisms of BM-MSCs infusion in high fat diet/streptozotocin (HFD/STZ)-induced T2DM rats. Thirty male Wistar rats were divided into 3 groups: Normal control, T2DM, and T2DM treated with BM-MSCs. The anti-diabetic effect of BM-MSCs was evidenced by ameliorating the state of hyperglycemia, hyperinsulinemia, and hyperlipidemia. BM-MSCs enhanced significantly insulin sensitivity in diabetic rats via decreasing leptin levels in serum and consequently, increasing adiponectin/leptin ratio, compared to T2DM group. Furthermore, BM-MSCs improved glucose homeostasis by up-regulating gene expressions of hepatic glucokinase and glycogen synthase in the liver and skeletal muscles as well as increasing their levels. Treatment of T2DM with BM-MSCs stimulated pancreatic regeneration in diabetic rats by up-regulating the expression of insulin-like growth factor-1 receptor gene, compared to diabetic and normal control groups. Histopathological results show that BM-MSCs therapy ameliorated HFD/STZ-induced atrophy in islands of Langerhans cells with the presence of mild cystic dilatation in the duct system. In conclusion, BM-MSCs might be an ideal therapeutic option for T2DM since they ameliorated peripheral insulin resistance and promoted beta cell regeneration.