STUDIES ON THE MECHANISMS OF SOMATOSTATIN ACTION ON INSULIN RELEASE

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Abstract
The effects of somatostatin on insulin release and cyclic[c]AMP metabolism were studied in collagenase-isolated islets of Langerhans from the rat. Concentrations from 500 to 2000 ng/ml significantly inhibited glucose stimulated insulin release, while 100 and 200 ng/ml were ineffective. Somatostatin (2000 ng/ml) inhibited insulin release and [3H]-cAMP accumulation induced by 16.7 mM glucose after 10 and 30 min of incubation. In dose-response studies, the inhibition by somatostatin of the effect of glucose on [3H]cAMP and insulin release could be overcome by a high concentration of the hexose (44.9 mM), suggesting competitive inhibition. In the absence of glucose, somatostatin inhibited [3H]cAMP accumulation induced by the phosphodiesterase inhibitor, IBMX[3-isobutyl-1-methylxanthine], while no inhibition was seen, again in the absence of hexose, when the [3H]cAMP levels had been raised by the adenyl cyclase stimulator, cholera toxin. Somatostatin did not affect phosphodiesterase activity when added to islet homogenates, but preincubation of the islets with the peptide before homogenization decreased the activity by about 30%. Somatostatin-induced inhibition of insulin release may be, at least partially, mediated by cAMP, probably through an action on islet adenyl cyclase.