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ludc web

Lena Eliasson

Principal investigator

ludc web

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 of 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