Regulation of insulin secretion by cAMP in rat islets of Langerhans permeabilised by high‐voltage discharge

Abstract

Adenosine 3',5-cyclic monophosphate (CAMP) was shown to stimulate ins&in secretion from electrically permeabilised islets of Langerhans incubated in Ca2+/EGTA buffers. CAMP-induced insulin secretion occurred in the presence of either sub-stimulatory (50 nM) or stimulatory (> 100 nM) concentrations of Ca2+.Similar effects on secretion were obtained in response to I-bromo-CAMP (8-Br-CAMP) or the phosphodiesterase inhibitor, 3-isobutyl-l-methylxanthine. Forskolin (0.2-20 PM) increased adenylate cyclase activity and enhanced insulin secretion from the ~~eabili~ islets. These results suggest that, in electrically permeabilised islets, CAMP-indu~d insulin secretion is not dependent on changes in cytosohc Ca2+. Insulin secretion (Islets of Langerhans)Electrical permeabilization cyclic AMP Forskolin Isobutylmethylxanthine

Catecholamine inhibition of Ca2+‐induced insulin secretion from electrically permeabilised islets of Langerhans

“…However, the small but significant secretory responses of permeabilised islets to cAMP at substimulatory Ca 2+ concentrations were not affected by noradrenaline, perhaps suggesting that catecholamines preferentially inhibit the normal secretory responses of permeabilised B-cells to Ca 2+, rather than to cAMP. cAMP is generally thought not to be an initiator of insulin secretion, but to modulate the magnitude of the B-cell secretory response to primary stimuli (see [21]), perhaps by increasing the sensitivity of the secretory process to Ca 2+ [10,28]. It is therefore slightly surprising that cAMP stimulated insulin secretion from noradrenaline-treated permeabilised islets which no longer responded to Ca 2+.…”

“…Electrically permeabilised islets do not respond to glucose [8] but secrete insulin in response to Ca 2÷ [91 or cAMP [10], and thus offer a useful model in which to study the involvement of these intracellular mediators in the control of insulin secretion.…”

Oscillatory control of insulin secretion

“…Early studies demonstrated that cAMP amplifies secretion in response to various initiators by promoting electrical activity and Ca 2+ signals (Gylfe and Hellman, 1981;Henquin and Meissner, 1984;Eddlestone et al, 1985;Hellman et al, 1992), as well as by sensitizing the secretory machinery to Ca 2+ (Tamagawa et al, 1985;Jones et al, 1986;Hellman et al, 1992).…”

β-Cell Mitochondria and Insulin Secretion

“…This paracrine effect of glucagon was also recently demonstrated in human islets (31). cAMP exerts at least three actions that may render the ␤-cell glucose-competent and enhance insulin secretion: 1) the Ca 2ϩ current through L-type Ca 2ϩ channels is increased (49); 2) ␤-cells refractory to glucose depolarization become responsive, showing K ATP -channel closure (50); and 3) the secretory machinery is sensitized to Ca 2ϩ (40,49,51,52). All these actions are mediated by cAMP-dependent protein kinase A.…”