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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
Publishing year: 2010
Language: English
Pages: 543-553
Publication/Series: Cell Metabolism
Volume: 11
Issue: 6
Document type: Journal article
Publisher: Cell Press

Abstract 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).

Keywords

  • Cell and Molecular Biology

Other

Published
  • Islet cell exocytosis
  • Islet cell physiology
  • Islet patophysiology
  • ISSN: 1550-4131
Erik Renström
E-mail: erik.renstrom [at] med.lu.se

Deputy head of department

Department of Clinical Sciences, Malmö

+46 40 39 11 57

+46 40 39 11 57

Principal investigator

Islet patophysiology

+46 40 39 11 57

+46 40 39 11 57

20-3-308

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Lund University Diabetes Centre, CRC, SUS Malmö, Entrance 72, House 91:12. SE-205 02 Malmö. Telephone: +46 40 39 10 00