The interaction between cAMP-dependent and cAMP-independent mechanisms in mediating the somatostatin inhibition of insulin secretion in isolated rat pancreatic islets

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Abstract
To characterize the intracellular mechanisms by which somatostatin modulates the insulin secretion, studies were performed with isolated rat pancreatic islets at 12 mmol l-1 glucose. Somatostatin (0.1-1000 nmol l-1) inhibited the glucose-induced insulin secretion concentration-dependently. Increasing intracellular cAMP concentration either with dibutyryl-cAMP (1 mmol l-1) or by the adenylate cyclase activator forskolin (20 mumol l-1) partly reversed the inhibition by somatostatin (100 nmol l-1). Neither somatostatin (100 nmol l-1) nor dibutyryl-cAMP (1 mmol l-1 were able to affect the low insulin secretion observed in the absence of extracellular Ca2+. To study cAMP-independent mechanisms of somatostatin, the experiments were performed with and without dibutyryl-cAMP (1 mmol l-1) present. Both somatostatin (100 nmol l-1) and the Ca(2+)-channel blocker verapamil (25 mumol l-1) inhibited the insulin secretion both with and without dibutyryl-cAMP present. An additional inhibition of the insulin secretion was observed when somatostatin was combined with verapamil in the absence, but not in the presence of dibutyryl-cAMP. We conclude that somatostatin inhibits the glucose-induced insulin secretion both by cAMP-dependent mechanism which requires extracellular Ca2+, and by cAMP-independent/verapamil-sensitive Ca(2+)-channel-dependent mechanism.

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