Studies on the mechanism of inhibition of glucose-stimulated insulin secretion by noradrenaline in rat islets of Langerhans

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Abstract
Noradrenaline (norepinephrine [NE]) was shown to be a potent inhibitor of glucose-induced insulin release from rat pancreatic islets, with half-maximal inhibition of the secretory response to 20 mM-glucose occurring at .apprx. 0.3 .mu.M, and complete suppression of the response occurring at 4 .mu.M-NE. Inhibition of insulin secretion by NE was antagonized by the .alpha.2-adrenergic antagonist yohimbine (half maximally effective dose .apprx. 1 .mu.M), but was largely unaffected by the .alpha.1-adrenergic antagonist prazosin at concentrations up to 50 .mu.M, suggesting that the response was mediated by .alpha.2-adrenergic receptors. NE significantly reduced the extent of 45Ca2+ accumulation in glucose-stimulated islets, although as much as 5 .mu.M-NE was required for 50% inhibition of this response. The ability of NE to inhibit islet-cell 45Ca2+ uptake was totally abolished in media containing 1 mM-dibutyryl cAMP, suggesting that the response may have been secondary to lowering of islet cAMP. Under these conditions, however, NE was still able to inhibit insulin secretion maximally. The data suggest that the site(s) at which NE acts to mediate inhibition of insulin secretion in rat islets lies distal to both islet-cell cAMP accumulation and Ca2+ uptake.