Exogenous obestatin decreases beta-cell apoptosis and alfa-cell proliferation in high fat diet and streptozotocin induced type 2 diabetic rats.

Type 2 diabetes is a chronic metabolic disease characterized by progressive decrease of islet cell function. Delaying the process of islet failure remains a challenging goal in diabetes care. Previous studies have confirmed the role of obestatin, a gut peptide that belongs to ghrelin family, in the mediation of glucose metabolism. This study aimed to observe the long term effects of exogenous obestatin on glucose metabolism in type 2 diabetes rat model. Type 2 diabetic rat model was set up by high-fat diet (60%) followed by a low dose of streptozotocin intra-peritoneal injection. Exogenous obestatin was administered at a dose of 20 nmol/kg for 12 weeks by intraperitoneal injection. Compared to placebo group (saline intraperitoneal injection), obestatin treatment decreased the glucagon levels and increased the c-peptide levels. Furthermore, obestatin treatment led to a significant restoration of islet morphology, increasing insulin and reducing glucagon expressions. Apoptosis assay showed a reduction in the number of TUNEL positive-cells. The up-regulation of Akt and GSK3β in pancreas was confirmed by Real-Time PCR. These results demonstrated that obestatin might have a potential therapeutic relevance in improving islet cell function, including increasing insulin secretion through inhibiting beta cell apoptosis and decreasing glucagon secretion by inhibiting alfa cell proliferation in type 2 diabetes. In spite of its role in these phenomena, it is necessary to further discuss, especially regarding the role of obestatin on glucagon.