A Novel Peptide COX52-69 Inhibits High Glucose-induced Insulin Secretion by Modulating BK Channel Activity

Background: Excessive insulin is the leading cause of metabolic syndromes besides hyperinsulinemia. Insulin-lowering therapeutic peptides have been poorly studied and warrant urgent attention. Objectives: The main purpose of this study, was to introduce a novel peptide COX52-69 that was initially isolated from the porcine small intestine and possessed the ability to inhibit insulin secretion under high-glucose conditions by modulating large conductance Ca²⁺-activated K⁺ channels (BK channels) activity. Methods and Results: Enzyme-linked immunosorbent assay results indicate that COX52-69 supressed insulin release induced by high glucose levels in pancreatic islets and animal models. Furthermore, electrophysiological data demonstrated that COX52-69 can increase BK channel currents and hyperpolarize cell membranes. Thus, cell excitability decreased, corresponding to a reduction in insulin secretion. Conclusion: Our study provides a novel approach to modulate high glucose-stimulated insulin secretion in patients with hyperinsulinemia.