Cyclic AMP raises cytosolic Ca2+ and promotes Ca2+ influx in a clonal pancreatic beta-cell line (HIT T-15).
The effect on cytosolic Ca2+ concentration ([Ca2+]i) of cAMP analogues and the adenylate cyclase-stimulating agents forskolin, isoproterenol and glucagon has been examined in an insulin-secreting beta-cell line (HIT T-15) using fura 2. All these manipulations of the cAMP messenger system promoted a rise in [Ca2+]i which was blocked by the Ca2+ channel antagonists verapamil and nifedipine or by removal of extracellular Ca2+. The action of the adenylate cyclase activator forskolin was glucose-dependent. The results suggest that cAMP elevates [Ca2+]i in HIT cells by promoting Ca2+ entry through voltage-sensitive Ca2+ channels, not through mobilization of stored Ca2+. Activation of Ca2+ influx may be an important component of the mechanisms by which cAMP potentiates fuel-induced insulin release.
D000818:Animals; D001572:Benzofurans / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D006224:Cricetinae; D000242:Cyclic AMP / Q000494:pharmacology*; D003600:Cytosol / Q000378:metabolism*; D004533:Egtazic Acid / Q000494:pharmacology; D016257:Fura-2; D007328:Insulin / Q000378:metabolism; D007473:Ion Channels / Q000187:drug effects; D007515:Islets of Langerhans / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology
D001572:Benzofurans; D007328:Insulin; D007473:Ion Channels; D005576:Colforsin; D004533:Egtazic Acid; D014700:Verapamil; D000242:Cyclic AMP; D002118:Calcium; D016257:Fura-2