Cortistatin regulates glucose-induced electrical activity and insulin secretion in mouse pancreatic beta-cells

Although there is growing evidence that cortistatin regulates several functions in different tissues, its role in the endocrine pancreas is not totally known. Here, we aim to study the effect of cortistatin on pancreatic beta-cells and glucose-stimulated insulin secretion (GSIS). Exposure of isolated mouse islets to cortistatin inhibited GSIS. This effect was prevented using a somatostatin receptor antagonist Additionally, cortistatin hyperpolarized the membrane potential and reduced glucose-induced action potentials in isolated pancreatic beta-cells. Cortistatin did not modify ATP-dependent K+ (K-ATP) channel activity. In contrast, cortistatin increased the activity of a small conductance channel with characteristics of G protein-coupled inwardly rectifying K+ (GIRK) channels. The cortistatin effects on membrane potential and GSIS were largely reduced in the presence of a GIRK channel antagonist and by down-regulation of GIRK2 with small interfering RNA. Thus, cortistatin acts as an inhibitory signal for glucose-induced electrical activity and insulin secretion in the mouse pancreatic beta-cell479123132CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ302261/2014-1; 306359/2017-0We thank M.S. Ramon and M.L. Navarro for their expert technical assistance, and R. Pérez-Rodríguez for her help with English. This work was supported by grants from the Ministerio de Economía, Industria y Competitividad (Spain), Agencia Estatal de Investigación (Spain) and Fondo Europeo de Desarrollo Regional (BFU2013-42789; BFU2017-86579-R; BFU2016-77125-R), Generalitat Valenciana (Spain, PROMETEOII/2015/016), CNPq (Brazil; 302261/2014-1; 306359/2017-0) and Junta de Andalucía (Spain; CTS-1406, BIO-0139). L.M. holds a Juan de la Cierva fellowship from the Ministry of Economy, Industry and Competitiveness (Spain; IJCI-2015-24482). CIBERDEM and CIBERobn are an initiative of the Instituto de Salud Carlos III (Spain