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

Sergi Soriano, Manuel Castellano-Muñoz, Alex Rafacho, Paloma Alonso-Magdalena, Laura Marroquí, Antonia Ruiz-Pino, Eva Bru-Tarí, Beatriz Merino, Esperanza Irles, Melisa Bello-Pérez, Pau Iborra, Sabrina Villar-Pazos, Jean F. Vettorazzi, Eduard Montanya, Raúl M. Luque, Ángel Nadal, Iván Quesada

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

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+ (KATP) 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-cell.

Original languageEnglish (US)
Pages (from-to)123-132
Number of pages10
JournalMolecular and cellular endocrinology
Volume479
DOIs
StatePublished - Jan 5 2019

Keywords

  • Cortistatin
  • GIRK channels
  • Insulin secretion
  • K channels
  • Pancreatic beta-cell

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

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