Your browser has javascript turned off or blocked. This will lead to some parts of our website to not work properly or at all. Turn on javascript for best performance.

The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Erik Renström

Erik Renström

Vice-chancellor

Erik Renström

GLP-1 inhibits and adrenaline stimulates glucagon release by differential modulation of N- and L-type Ca2+ channel-dependent exocytosis.

Author

  • Yang De Marinis
  • S Albert Salehi
  • Caroline E Ward
  • Quan Zhang
  • Fernando Abdulkader
  • Martin Bengtsson
  • Orit Braha
  • Matthias Braun
  • Reshma Ramracheya
  • Stefan Amisten
  • Abdella M Habib
  • Yusuke Moritoh
  • Enming Zhang
  • Frank Reimann
  • Anders Rosengren
  • Tadao Shibasaki
  • Fiona Gribble
  • Erik Renström
  • Susumu Seino
  • Lena Eliasson
  • Patrik Rorsman

Summary, in English

Glucagon secretion is inhibited by glucagon-like peptide-1 (GLP-1) and stimulated by adrenaline. These opposing effects on glucagon secretion are mimicked by low (1-10 nM) and high (10 muM) concentrations of forskolin, respectively. The expression of GLP-1 receptors in alpha cells is <0.2% of that in beta cells. The GLP-1-induced suppression of glucagon secretion is PKA dependent, is glucose independent, and does not involve paracrine effects mediated by insulin or somatostatin. GLP-1 is without much effect on alpha cell electrical activity but selectively inhibits N-type Ca(2+) channels and exocytosis. Adrenaline stimulates alpha cell electrical activity, increases [Ca(2+)](i), enhances L-type Ca(2+) channel activity, and accelerates exocytosis. The stimulatory effect is partially PKA independent and reduced in Epac2-deficient islets. We propose that GLP-1 inhibits glucagon secretion by PKA-dependent inhibition of the N-type Ca(2+) channels via a small increase in intracellular cAMP ([cAMP](i)). Adrenaline stimulates L-type Ca(2+) channel-dependent exocytosis by activation of the low-affinity cAMP sensor Epac2 via a large increase in [cAMP](i).

Department/s

  • Diabetes - Islet Cell Exocytosis
  • Islet cell physiology
  • Diabetes - Islet Patophysiology
  • EXODIAB: Excellence in Diabetes Research in Sweden

Publishing year

2010

Language

English

Pages

543-553

Publication/Series

Cell Metabolism

Volume

11

Issue

6

Document type

Journal article

Publisher

Cell Press

Topic

  • Cell and Molecular Biology

Status

Published

Research group

  • Diabetes - Islet Cell Exocytosis
  • Islet cell physiology
  • Diabetes - Islet Patophysiology

ISBN/ISSN/Other

  • ISSN: 1550-4131