Plasma Insulin in Organic Hyperinsulinism: Comparative Effects of Tolbutamide, Leucine and Glucose1

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Abstract
Concentrations of plasma insulin were determined in peripheral blood before and after the administration of tolbutamide, leucine, glucose and glucagon to 13 patients with insulinoma. Content or concentration, or both, of extractable insulin was determined in the tumors of 11 patients. The means of maximal increases in plasma insulin were excessive after tolbutamide (576 [mu]U/ml), after leucine (211[mu]U/ml) and after glucose (384[mu]U/ml). Small increases in concentrations of plasma leucine effected excessive increases in concentrations of plasma insulin in some of the patients with insulinoma. Concentrations of insulin in 11 tumors ranged from 0.02 to 60. 75 U/g. Patients whose tumors contained smaller amounts of insulin had lesser increments in plasma insulin after administration of tolbutamide, leucine and glucose and were more likely to have "falsely negative" blood glucose responses to tolbutamide. Hyperglycemia occurring after removal of an insulinoma was associated with hypoinsulinism and disappeared in the presence of normal levels of insulin in peripheral plasma. It is concluded that of the stimuli studied in patients with insulinoma, tolbutamide is the most potent one for insulin release. Although glucose may effect greater absolute increases in plasma insulin than does leucine, the increases after leucine distinguish better than those after glucose the abnormal from the normal response; the magnitude of increases in concentration of plasma insulin after administration of tolbutamide, leucine or glucose is related to the amount of insulin stored in the tumor; detection of excessive increments in concentrations of plasma insulin soon after administration of tolbutamide, leucine or glucose can be of aid in establishing a diagnosis of insulinoma; small increases in plasma leucine may cause release of excessive amounts of insulin from neoplastic beta cells; and both hypoinsulinism and factors counterregulatory to hypoglycemia can contribute to the hyperglycemia frequently observed after removal of an insulinoma.