GLP-1 inhibits and adrenaline stimulates glucagon release by differential modulation of N- and L-type Ca2+ channel-dependent exocytosis.
Författare
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).
Avdelning/ar
Publiceringsår
2010
Språk
Engelska
Sidor
543-553
Publikation/Tidskrift/Serie
Cell Metabolism
Volym
11
Issue
6
Fulltext
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
Cell Press
Ämne
- Cell and Molecular Biology
Status
Published
Forskningsgrupp
- Diabetes - Islet Cell Exocytosis
- Islet cell physiology
- Diabetes - Islet Patophysiology
ISBN/ISSN/Övrigt
- ISSN: 1550-4131