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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
1997-4-25
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pubmed:abstractText |
The mechanisms by which glucose-dependent insulinotropic polypeptide (GIP) stimulates insulin secretion were investigated by measurements of whole-cell Ca2+ currents, the cytoplasmic Ca2+ concentration, and cell capacitance as an indicator of exocytosis in individual mouse pancreatic beta-cells maintained in short-term culture. GIP produced a 4.2-fold potentiation of depolarization-induced exocytosis. This stimulation of exocytosis was not associated with a change in the whole-cell Ca2+-current, and there was only a small increase (30%) in the cytoplasmic Ca2+ concentration [intercellular free Ca2+([Ca2+]i)]. The stimulatory effect of GIP on exocytosis was blocked by pretreatment with the specific protein kinase A (PKA) inhibitor Rp-8-Br-cAMPS. Glucagon-like peptide-I(7-36) amide (GLP-I) stimulated exocytosis (90%) in the presence of a maximal GIP concentration (100 nmol/l). Replacement of GLP-I with forskolin produced a similar stimulatory action on exocytosis. These effects of GLP-I and forskolin in the presence of GIP did not involve a change in the whole-cell Ca2+-current or [Ca2+]i. GIP was ineffective in the presence of both forskolin and the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX). Under the same experimental conditions, the protein kinase C (PKC)-activating phorbol ester 4-phorbol 12-myristate 13-acetate (PMA) stimulated exocytosis (60%). Collectively, our data indicate that the insulinotropic hormone GIP stimulates insulin secretion from pancreatic beta-cells, through the cAMP/PKA signaling pathway, by interacting with the secretory machinery at a level distal to an elevation in [Ca2+]i.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/1-Methyl-3-isobutylxanthine,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Forskolin,
http://linkedlifedata.com/resource/pubmed/chemical/Gastric Inhibitory Polypeptide,
http://linkedlifedata.com/resource/pubmed/chemical/Gastrointestinal Hormones,
http://linkedlifedata.com/resource/pubmed/chemical/Glucagon,
http://linkedlifedata.com/resource/pubmed/chemical/Glucagon-Like Peptide 1,
http://linkedlifedata.com/resource/pubmed/chemical/Glucagon-Like Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphodiesterase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate,
http://linkedlifedata.com/resource/pubmed/chemical/Thionucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/adenosine-3',5'-cyclic...,
http://linkedlifedata.com/resource/pubmed/chemical/glucagon-like peptide 1 (7-36)amide
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0012-1797
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
46
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
615-21
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:9075801-1-Methyl-3-isobutylxanthine,
pubmed-meshheading:9075801-Animals,
pubmed-meshheading:9075801-Calcium,
pubmed-meshheading:9075801-Cell Membrane,
pubmed-meshheading:9075801-Cells, Cultured,
pubmed-meshheading:9075801-Cyclic AMP,
pubmed-meshheading:9075801-Cyclic AMP-Dependent Protein Kinases,
pubmed-meshheading:9075801-Dose-Response Relationship, Drug,
pubmed-meshheading:9075801-Electric Conductivity,
pubmed-meshheading:9075801-Enzyme Inhibitors,
pubmed-meshheading:9075801-Exocytosis,
pubmed-meshheading:9075801-Forskolin,
pubmed-meshheading:9075801-Gastric Inhibitory Polypeptide,
pubmed-meshheading:9075801-Gastrointestinal Hormones,
pubmed-meshheading:9075801-Glucagon,
pubmed-meshheading:9075801-Glucagon-Like Peptide 1,
pubmed-meshheading:9075801-Glucagon-Like Peptides,
pubmed-meshheading:9075801-Islets of Langerhans,
pubmed-meshheading:9075801-Membrane Potentials,
pubmed-meshheading:9075801-Mice,
pubmed-meshheading:9075801-Mice, Inbred Strains,
pubmed-meshheading:9075801-Peptide Fragments,
pubmed-meshheading:9075801-Phosphodiesterase Inhibitors,
pubmed-meshheading:9075801-Tetradecanoylphorbol Acetate,
pubmed-meshheading:9075801-Thionucleotides
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pubmed:year |
1997
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pubmed:articleTitle |
Protein kinase A-dependent stimulation of exocytosis in mouse pancreatic beta-cells by glucose-dependent insulinotropic polypeptide.
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pubmed:affiliation |
Department of Islet Cell Physiology, Novo Nordisk A/S, Copenhagen, Denmark.
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pubmed:publicationType |
Journal Article,
Comparative Study
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