Influence of the sympatho-adrenal system and somatostatin on the secretion of insulin in the rat.

Abstract

1. The effects of somatostatin on insulin secretion in anaesthetized rats subjected to different manipulations of the sympatho-adrenal system have been investigated.2. Somatostatin (0.1 mug/min) inhibited the secretion of insulin in intact rats both in the basal state and after inducing an enhanced insulin release by infusion of the alpha-adrenoceptor-blocker phentolamine.3. Combined surgical splanchnicotomy and adrenalectomy caused an increase in the basal plasma insulin concentration. Somatostatin (0.1 mug/min) inhibited basal insulin release also in these rats. After infusion of phentolamine, however, the dose of somatostatin had to be raised five fold (0.5 mug/min) to achieve a comparable inhibition of insulin release. On the other hand, a similar rate of insulin secretion induced by glucose in intact rats could be inhibited by the lower dose of somatostatin.4. Administration of the beta-adrenoceptor-blocking agent propranolol to splanchnicotomized-adrenalectomized rats lowered basal insulin secretion to the same level as seen in intact rats. In these beta-adrenoceptor-blocked rats somatostatin (0.1 mug/min) inhibited insulin release both in the presence and absence of alpha-adrenoceptor blockade.5. Rats subjected to chemical sympathectomy through pre-treatment with 6-hydroxydopamine together with adrenalectomy displayed plasma insulin concentrations slightly above the normal range, but the values were much lower than in splanchnicotomized-adrenalectomized rats. Infusion of phentolamine to the chemically sympathectomized rats did not further increase insulin secretion, and somatostatin (0.1 mug/min) depressed insulin release both in the absence and presence of alpha-adrenoceptor blockade.6. It is suggested that an inhibitory tone exerted by the splanchnic nerves modulates the basal insulin secretion in the rat. Somatostatin and the sympathoadrenal system show a complex interaction on the insulin cells in that the sensitivity to somatostatin in splanchnicotomized-adrenalectomized rats with intact beta-adrenoceptors is decreased in the presence of the alpha-adrenoceptor-blocker phentolamine. The exact mechanism behind this decreased sensitivity remains unclear.