Adrenalectomy and chemical sympathectomy by 6-hydroxydopamine. Effects on basal and stimulated insulin secretion.

Influences of the sympatho-adrenal system on basal and stimulated insulin secretion were studied in vivo in the conscious mouse and rat. In the mouse, adrenalectomy or chemical sympathectomy, induced by 6-hydroxydopamine, lowered basal insulin concentrations moderately. A marked depression of basal insulin concentration (about 50%) was seen after the combined treatment of chemical sympathectomy and adrenalectomy. In short-term experiments in mice, insulin secretion stimulated by glucose or the cholinergic agonist carbachol was enhanced after chemical sympathectomy and/or adrenalectomy, whereas insulin release induced by the synthetic octapeptide of cholecystokinin (CCK-8) was inhibited. The promoting influences on the insulin secretory response to carbachol displayed a rapid development whereas those to glucose developed more slowly. In contrast, the inhibiting effect on CCK-8 stimulated insulin release vanished with time. The insulin secretory response to the beta 2-adrenoceptor stimulator, terbutaline, was increased after chemical sympathectomy, unaffected by adrenalectomy, and decreased after chemical sympathectomy plus adrenalectomy. The glucose elimination rate after 6 weeks of chemical sympathectomy was increased in mice and decreased in rats. The insulin secretory response to glucose was enhanced in mice, whereas it tended to diminish in rats after long-term sympathectomy. In conclusion, the sympatho-adrenal system is involved in regulation of basal insulin concentrations in the mouse, and apparently is of great importance for stimulated insulin secretion; the influence being dependent on the nature of the secretagogue.