No abstract

The purpose of this study was to determine if increased concentrations of pancreatic islet norepinephrine, dopamine, or serotonin after insulin secretion. Golden hamsters received intraperitoneal injections of the norepinephrine precursor DL-threo-dihydroxyphenylserine, the dopamine precursor L-3,4-dihydroxyphenylalanine, or the serotonin precursor 5-hydroxytryptophan with and without pretreatment of the hamsters with the monoamine oxidase inhibitor tranylcypromine. Administration of the monoamine precursors to animals pretreated with tranylcypromine resulted in a mean increase in plasma glucose of 192% and a mean decrease in plasma insulin of 58%. Using a collagenase isolation technique, islets from control and treated animals were evaluated for monoamine content and insulin secretory capacity. The monoamine concentrations in control islets, in mumol/kg wet weight, were: norepinephrine 42 +/- 8; dopamine 8 +/- 2; and serotonin 26 +/- 9. Administration of the appropriate precursor to control hamsters resulted in a 1.9-fold (norepinephrine), 6-fold (dopamine), and 22-fold (serotonin) increase in monoamines. There was no alteration in the glucose (16.3 mmol/l)-stimulated in vitro insulin secretion from islets obtained from these hamsters. Administration of the precursors to hamsters pretreated with tranylcypromine resulted in a 3.5-fold (norepinephrine), 22-fold (dopamine), and 59-fold (serotonin) increase in monoamines. Glucose-stimulated in vitro insulin secretion from islets obtained from these hamstes was completely blocked. This study suggest that high concentrations of norepinephrine, dopamine, and serotonin in the pancreatic islets can decrease glucose-stimulated insulin secretion.

No abstract

The catecholamines norepinephrine (NE) and dopamine (DA), known inhibitors of insulin secretion, have been identified in the pancreatic islets only semiquantitatively by their histochemical fluorescence spectrum. Using collagenase digestion of golden hamster pancreas, we isolated islets and quantitated the NE and DA content with sensitive and specific radioenzymatic assays. We compared the NE and DA concentrations in islets with the median eminence and cerebral cortex of the golden hamster, tissues known to contain catecholamines. Under basal conditions, NE is in higher concentration than DA in all three tissues and is highest in the islets in a much greater concentration than is found in the median eminence. DA is present in measurable quantities in all three tissues and, in the islets, its concentration is comparable with that in the median eminence.Treatment of the hamster with a precursor of the two catecholamines, L-dopa, produced a significant accumulation of DA in the islets and median eminence over the basal values. This L-dopa-induced increase in DA was heightened in the islets and reached significantly higher than control levels in the cortex by a pretreatment of the hamster with tranylcypromine (tran), a monomine oxidase inhibitor. Pretreatment with tran alone, however, produced no change in DA over control values.The NE content of pancreatic islets was not altered by administration of L-dopa, tran, or L-dopa plus tran. The NE content of the median eminence was increased by the administration of tran. L-dopa plus tran did not result in an additional increase in the NE content of the median eminence. The administration of tran plus L-dopa (but not the administration of either agent alone) increased the NE content of the cortex over control levels. The present study suggests that inhibition of insulin secretion From the Durham Veterans after L-dopa administration is due to an increased concentration of DA rather than NE in the pancreatic islets. DIABETES 28:185-189, March 1979.T hirty years ago, Sawyer, Markee, and Hollinshead first proposed a mechanism for hormone release in the anterior pituitary that depended on catecholamines. 1 Functional studies of the activity of the catecholamine system with certain endocrinologic changes 2 and further investigations with fiuorescenceimmunocytochemical techniques localizing the catecholamine storage sites 3 have established the importance of catecholamines in regulating hormone secretion. In 1963, biogenic amines were identified in the pancreatic islets of Langerhans of different species by formaldehyde-induced fluorescence. 4 Since then, precise subcellular localization of these biogenic amines to the hormone-containing granules 5 " 7 lead directly to exciting considerations of their physiologic roie in the endocrine pancreas. Some investigators have demonstrated that exogenous dopamine and serotonin inhibit in vivo and in vitro insulin release stimulated by a variety of agents in certain species. 6>8 -9~u Other investigators have shown these two amines to stim...