Chronic orexin-a (Hypocretin-1) treatment of type 2 diabetic rats improves glucose control and beta-cell functions

Orexin regulates food intake and energy expenditure. here,we test the ability of orexin-a (oxa,hypocretin-1) at improving metabolic control in type 2 diabetic animals and elaborate potential mechanisms of action. rats with experimentally induced type 2 diabetes by a combination of streptozotocin injection and high-fat diet feeding were chronically infused with oxa. in vitro experiments were conducted on isolated pancreatic islets,primary adipocytes and insulin secreting ins-1e cells. oxa improved glucose control,enhanced insulin sensitivity and attenuated pancreatic β-cell loss in type 2 diabetic rats. ex vivo,apoptotic death of pancreatic islets isolated from oxa-treated type 2 diabetic animals as well as the impairment of glucose-stimulated insulin secretion were attenuated,as compared to islets derived from vehicle-treated rats. oxa reduced plasma tumor necrosis factor-α (tnf-α) and non-esterified fatty acids (nefa) levels in type 2 diabetic rats. oxa decreased palmitate- and tnf-α-induced apoptosis of ins-1e cells. oxa improves glucose control by enhancing insulin sensitivity and protecting β-cells from apoptotic cell death in type 2 diabetic animals. © 2017,polish physiological society. all rights reserved.