Glucagon-like peptide 1 (7-36) amide stimulates exocytosis in human pancreatic beta-cells by both proximal and distal regulatory steps in stimulus-secretion coupling.

Journal article

The effect of glucagon-like peptide 1(7-36) amide [GLP-1(7-36) amide] on membrane potential, whole-cell ATP-sensitive potassium channel (K[ATP]) and Ca2+ currents, cytoplasmic Ca2+ concentration, and exocytosis was explored in single human beta-cells. GLP-1(7-36) amide induced membrane depolarization that was associated with inhibition of whole-cell K(ATP) current. In addition, GLP-1(7-36) amide (and forskolin) produced greater than fourfold potentiation of Ca2+-dependent exocytosis. The latter effect resulted in part (40%) from acceleration of Ca2+ influx through voltage-dependent (L-type) Ca2+ channels. More importantly, GLP-1(7-36) amide (via generation of cyclic AMP and activation of protein kinase A) potentiated exocytosis at a site distal to a rise in the cytoplasmic Ca2+ concentration. Photorelease of caged cAMP produced a two- to threefold potentiation of exocytosis when the cytoplasmic Ca2+ concentrations were clamped at > or =170 nmol/l. The effect of GLP-1(7-36) amide was antagonized by the islet hormone somatostatin. Similar effects on membrane potential, ion conductances, and exocytosis were observed with glucose-dependent insulinotropic polypeptide (GIP), the second major incretin. The present data suggest that the strong insulinotropic action of GLP-1(7-36) amide and GIP in humans results from its interaction with several proximal as well as distal important regulatory steps in the stimulus-secretion coupling.

Authors: Gromada, J; Bokvist, K; Ding, W; Holst, J; Nielsen, J

• Publication status: Published
• Journal: Diabetes
• Volume: 47
• Issue: 1
• Pages: 57-65
• Publication date: 1998-01-01
• DOI: 10.2337/diab.47.1.57
• EISSN: 1939-327X
• ISSN: 0012-1797
• Language: English
• Keywords: Potassium Channels; Calcium; Adult; Forskolin; Humans; Glucagon; Membrane Potentials; Exocytosis; Male; Cyclic AMP; Islets of Langerhans; Middle Aged; Peptide Fragments; Cells, Cultured; Female; Gastric Inhibitory Polypeptide; Glucagon-Like Peptides; Neurotransmitter Agents; Glucagon-Like Peptide 1; Cyclic AMP-Dependent Protein Kinases; Somatostatin; Calcium Channels