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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
7
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pubmed:dateCreated |
1989-8-8
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pubmed:abstractText |
With a glucose-responsive beta-cell line (HIT cells), we tested the hypothesis that the cytosolic free-Ca2+ level ([Ca2+]i) is an intracellular signal through which a rise in cyclic AMP (cAMP) levels is transmitted to potentiate glucose-stimulated insulin secretion. In these cells, glucose stimulates the acute release of insulin without increasing [Ca2+]i or altering cAMP content. Either forskolin or 3-isobutylmethylxanthine (IBMX) potentiated glucose-stimulated insulin secretion and increased cAMP levels. At either a submaximal glucose concentration or maximally stimulatory glucose concentration, both IBMX and forskolin triggered a rapid rise in [Ca2+]i (1.9- and 1.5-fold increase over basal levels, respectively). Similarly, glucagon stimulated a 1.3-fold increase in [Ca2+]i over basal levels. The effect on [Ca2+]i required glucose and was secondary to Ca2+ influx through voltage-dependent Ca2+ channels because it was blocked by either chelation of extracellular Ca2+ with EGTA or by the Ca2+-channel blockers verapamil and nimodipine. Verapamil also inhibited IBMX potentiation of glucose-stimulated insulin secretion and the IBMX-induced rise in [Ca2+]i in a dose-dependent manner with IC50s of 2 x 10(-5) and 4 x 10(-6) M, respectively. We conclude that in the beta-cell, a rise in cAMP levels increases Ca2+ influx through voltage-dependent Ca2+ channels and that this represents a mechanism by which cAMP potentiates glucose-stimulated insulin secretion in beta-cells.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
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/Benzofurans,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Forskolin,
http://linkedlifedata.com/resource/pubmed/chemical/Fura-2,
http://linkedlifedata.com/resource/pubmed/chemical/Glucagon,
http://linkedlifedata.com/resource/pubmed/chemical/Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Verapamil
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0012-1797
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
38
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
874-80
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:2472299-1-Methyl-3-isobutylxanthine,
pubmed-meshheading:2472299-Animals,
pubmed-meshheading:2472299-Benzofurans,
pubmed-meshheading:2472299-Calcium,
pubmed-meshheading:2472299-Calcium Channels,
pubmed-meshheading:2472299-Cell Line,
pubmed-meshheading:2472299-Cells, Cultured,
pubmed-meshheading:2472299-Cyclic AMP,
pubmed-meshheading:2472299-Electrophysiology,
pubmed-meshheading:2472299-Forskolin,
pubmed-meshheading:2472299-Fura-2,
pubmed-meshheading:2472299-Glucagon,
pubmed-meshheading:2472299-Glucose,
pubmed-meshheading:2472299-Insulin,
pubmed-meshheading:2472299-Islets of Langerhans,
pubmed-meshheading:2472299-Second Messenger Systems,
pubmed-meshheading:2472299-Verapamil
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pubmed:year |
1989
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pubmed:articleTitle |
Effect of rise in cAMP levels on Ca2+ influx through voltage-dependent Ca2+ channels in HIT cells. Second-messenger synarchy in beta-cells.
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pubmed:affiliation |
Department of Medicine, Baylor College of Medicine, Houston, TX 77030.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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