Current Protein & Peptide ScienceCurrent Protein & Peptide ScienceCurrent Protein & Peptide Science1389-20371875-5550Bentham Science64563410.2174/0113892037249620231010063637Life SciencesResearch ArticleA Novel Peptide COX52-69 Inhibits High Glucose-induced Insulin Secretion by Modulating BK Channel ActivityLinQianinfo@benthamscience.netLiuJingtaoinfo@benthamscience.netChenHenglinginfo@benthamscience.netHuWenwuinfo@benthamscience.netLeiWeiqionginfo@benthamscience.netWangMeijieinfo@benthamscience.netLinXianguanginfo@benthamscience.netZhangYongninginfo@benthamscience.netAiHuitinginfo@benthamscience.netChenSuinfo@benthamscience.netLiChenhonginfo@benthamscience.netLaboratory of Membrane Ion Channels and Medicine, Key Laboratory of Cognitive Science of State Ethnic Affairs Commission, Hubei Key Laboratory of Medical Information Analysis and Tumor Diagnosis and Treatment, College of Biomedical Engineering, South-Central Minzu UniversityLaboratory of Membrane Ion Channels and Medicine, Key Laboratory of Cognitive Science of State Ethnic Affairs Commission, Hubei Key Laboratory of Medical Information Analysis and Tumor Diagnosis and Treatment, College of Biomedical Engineering,, South-Central Minzu UniversityLaboratory of Membrane Ion Channels and Medicine, Key Laboratory of Cognitive Science of State Ethnic Affairs Commission, Hubei Key Laboratory of Medical Information Analysis and Tumor Diagnosis and Treatment, College of Biomedical Engineering, South-Central Minzu University,Laboratory of Membrane Ion Channels and Medicine, Key Laboratory of Cognitive Science of State Ethnic Affairs Commission, Hubei Key Laboratory of Medical Information Analysis and Tumor Diagnosis and Treatment, College of Biomedical Engineering,, South-Central Minzu University,0105202425541942611012025Copyright ©; 2024, Bentham Science Publishers2024Bentham Science Publishershttps://journals.eco-vector.com/1389-2037/article/view/645634

Background:Excessive insulin is the leading cause of metabolic syndromes besides hyperinsulinemia. Insulin-lowering therapeutic peptides have been poorly studied and warrant urgent attention.

Objective: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.

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