Tolbutamide, glucose, calcium, and somatostatin secretion

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Abstract
The actions of tolbutamide were studied on the release of somatostatin, insulin and glucagon from the isolated, perfused dog pancreas. Tolbutamide (180 .mu.M) elicited a biphasic response of all 3 islet hormones in the absence of glucose. In the presence of normal glucose (5.5 mM), 180 .mu.M to tolbutamide was again stimulatory, however, now the D cell response appeared uniphasic and the relative increase of somatostatin was lower than in the absence of glucose. At the highest perfusat glucose of 11 mM, no augmentation of the somatostatin output was seen to 180 .mu.M tolbutamide; the B and A cell secretion was still stimulated. In dose-response studies with tolbutamide (1.8-1800 .mu.M) the D cell threshold to tolbutamide was 18 .mu.M. Maximal D cell secretion was attained in the presence of 180 .mu.M tolbutamide at low glucose (1.4 mM) and of 18 .mu.M tolbutamide at normal glucose (5.5 mM), respectively. The insulin and glucagon responses showed clear-cut dose-dependency over the range of tolbutamide doses applied. The B and A cell threshold to tolbutamide was 1.8 .mu.M when the prevailing glucose level was stimulatory for the B and A cell, respectively. The finding that D and B cell responses to tolbutamide were eliminated during Ca deprivation indicates a key role of Ca in the events that proceeds to tolbutamide-mediated somatostatin and insulin release. The primary effect of tolbutamide on the islet cells is to stimulate hormone secretion, however, pertubations in terms of appearance and magnitude of D, B and A cell responses depend on the balance between the concentrations of tolbutamide and glucose.