We have demonstrated previously that spontaneously diabetic BB-Wistar rats exhibit decreased adrenal medullary catecholamine secretion in response to splanchnic nerve terminal stimulation. We hypothesized that this abnormality is caused by changes in the sensitivity of the adrenomedullary chromaffin cells to acetylcholine (ACh). To study this hypothesis, we isolated adrenal glands from control and spontaneously diabetic BB-Wistar rats, perfused them with ACh, and measured catecholamine secretion. Adrenal catecholamine release in response to ACh was significantly decreased at 2, 8, and 16 weeks after the onset of diabetes compared with age-matched, nondiabetic control rats. Catecholamine release in response to perfusion with 20 mM K+ was the same in adrenals from diabetic and control rats. The decreased responsiveness of diabetic rat adrenals to perfusion with ACh was significantly correlated with a decrease in the release of catecholamines in response to splanchnic nerve stimulation. A similar defect in catecholamine secretion was also seen in adrenals harvested from nondiabetic BB-Wistar rats following a 3-h period of acute hypoglycemia; however, the adrenal response to potassium was also decreased as was the catecholamine content of the adrenal. Conversely, nondiabetic BB-Wistar rats made diabetic with streptozocin (STZ) and maintained in a hyperglycemic state did not exhibit catecholamine hyposecretion 2 weeks after STZ administration. Collectively, the data describe decreased adrenomedullary response to cholinergic stimulation in spontaneously diabetic rats as early as 2 weeks after the onset of diabetes and that a similar, although more severe, hyposecretion occurs after acute, severe hypoglycemia.

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