Mechanism of orexin B-stimulated insulin and glucagon release from the pancreas of normal and diabetic rats

Objectives: To examine the pattern of distribution and effect of orexin B in the islets of normal and diabetic rats. Methods: 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. Results: 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. Conclusions: 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.