The Research Of The Mechanism Of A New Short Peptide COX_52-69 Inhibition Of Glucose-induced Insulin Secretion

Hyperinsulinemia is defined as a disease of high insulin levels in the blood,which is the basis of coronary heart disease,hypertension,hyperlipidemia,type II diabetes,and obesity.In recent years,the high incidence of the disease and its complications has attracted widespread attention.However,people have not found a good treatment.Therefore,finding a safe and effective treatment is a direction of the current research field.A new short peptide named COX_52-69 was isolated from the small intestine of the pig in the early stage of the laboratory and we found that it inhibited glucose-induced insulin secretion.We chemically synthesized the short peptide and found that the chemically synthesized short peptide COX_52-69 also inhibited glucose-induced insulin secretion by in vivo and in vitro islet level experiments.To explore the mechanism by which the short peptide COX_52-69 inhibited glucose-induced insulin secretion,we monitored and captured more than 90 proteins interacting with the short peptide COX_52-69 in islet?cells in real time using a drug target capture technique based on surface plasmon resonance?SPR?and microfluidic biochips.Then we screened for protein Kcnma1,which may play an important role in inhibiting glucose-induced insulin secretion by bioinformatics-related techniques.After semi-quantitative PCR experiments,we found that the expression level of Kcnma1 at mRNA level was significantly up-regulated in the COX_52-69 treatment group.Since Kcnma1 is a gene encoding the BK channel subfamily M subunit?,we then recorded the BK channel on islet?cells by whole-cell patch clamp.The results showed that COX_52-69 significantly increased the BK current of islet?cells,meant that the short peptide COX_52-69 inhibited glucose-induced insulin secretion by activating the BK channel.Many substances regulate insulin secretion by regulating the opening of K_ATPTP channels.This study shows that the short peptide COX_52-69 is rarely regulated by activating BK channels,and its mechanism maybe due to the opening of BK channels causes hyperpolarization or repolarization of cell membranes,inhibits depolarization,reduces excitability,and reduces the release of action potentials,thereby reducing insulin secretion.In addition,the BK channel is associated with the cGMP-PKG signaling pathway,which leads us to speculate that COX_52-69 influences the opening of BK channel through this signaling pathway.Therefore,the research of this subject lays a foundation for the action mechanism of COX_52-69 and increases the possibility of short peptide COX_52-69 in the treatment of hyperinsulinemia.