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
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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. / Gromada, J; Bokvist, K; Ding, W G; Holst, J J; Nielsen, Jens Høiriis; Rorsman, P.
In: Diabetes, Vol. 47, No. 1, 1998, p. 57-65.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - 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
AU - Gromada, J
AU - Bokvist, K
AU - Ding, W G
AU - Holst, J J
AU - Nielsen, Jens Høiriis
AU - Rorsman, P
PY - 1998
Y1 - 1998
N2 - 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.
AB - 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.
KW - Adult
KW - Calcium
KW - Calcium Channels
KW - Cells, Cultured
KW - Cyclic AMP
KW - Cyclic AMP-Dependent Protein Kinases
KW - Exocytosis
KW - Female
KW - Forskolin
KW - Gastric Inhibitory Polypeptide
KW - Glucagon
KW - Glucagon-Like Peptide 1
KW - Glucagon-Like Peptides
KW - Humans
KW - Islets of Langerhans
KW - Male
KW - Membrane Potentials
KW - Middle Aged
KW - Neurotransmitter Agents
KW - Peptide Fragments
KW - Potassium Channels
KW - Somatostatin
M3 - Journal article
C2 - 9421375
VL - 47
SP - 57
EP - 65
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 1
ER -
ID: 206915