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

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).

• 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
• 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
• Full text: - 2 MB; Download statistics
• Links: http://www.ncbi.nlm.nih.gov/pubmed/20519125?dopt=Abstract; http://dx.doi.org/10.1016/j.cmet.2010.04.007
• 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