Mechanism of Orexin B-Stimulated Insulin and Glucagon Release From the Pancreas of Normal and Diabetic Rats

Abstract

To examine the pattern of distribution and effect of orexin B in the islets of normal and diabetic rats. Pancreatic tissue fragments collected from normal and diabetic (4 weeks after the onset of diabetes) rats were either processed for immunohistochemistry or treated with different concentrations (10 to 10 mol/L) of orexin B. Orexin B-positive nerves were observed in the wall of blood vessels of both normal and diabetic rat pancreas. Orexin B is abundant in the islets of normal rats and colocalized with insulin in β cells. The number of orexin B-positive cells decreased after the onset of diabetes. Orexin B evoked significant (P<0.05) increases in insulin release from the pancreas of normal and diabetic rats. Propranolol, a β-adrenergic receptor antagonist, significantly (P<0.04) reduced the stimulatory effect of orexin B on insulin secretion. Orexin B also induced significant (P<0.05) increases in glucagon release from the pancreas of normal rats but failed to stimulate glucagon secretion from the pancreas of diabetic rats. Orexin B stimulated insulin secretion in normal and diabetic rat pancreas through the β-adrenergic pathway. Orexin B may have an important role in the regulation of islet function.