Alpha-adrenergic inhibition of rat pancreatic beta-cell replication and insulin secretion is mediated through a pertussis toxin-sensitive G-protein regulating islet cAMP content.
The rate of DNA synthesis, insulin secretion and cAMP content in isolated pancreatic islets were markedly inhibited by long-term exposure to the alpha 1-adrenoceptor agonist phenylephrine, the alpha 2-adrenoceptor agonist clonidine and the beta-adrenoceptor antagonist propranolol. Pertussis toxin or the stimulatory cAMP analog Sp-cAMPS increased DNA synthesis and insulin secretion in the absence of the adrenergic agents. Pertussis toxin blocked the inhibitory actions of these agents on DNA synthesis, insulin secretion and cAMP content, and a similar protection was imposed by Sp-cAMPS. Thus, long-term alpha-adrenergic stimulation interferes with signaling through pertussis toxin-sensitive G-protein(s) and, by decreasing the islet cAMP content, inhibits beta-cell DNA synthesis and insulin secretion.
Department of Medical Cell Biology, Uppsala University, Sweden.
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Sjöholm
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism*; D004247:DNA / Q000096:biosynthesis*; D019204:GTP-Binding Proteins / Q000187:drug effects; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D037342:Pertussis Toxin; D011863:Radioimmunoassay; D051381:Rats; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D007328:Insulin; D010566:Virulence Factors, Bordetella; D004247:DNA; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins