Enhancement of Insulin Secretion in Adult Onset Diabetics by Methysergide Maleate: Evidence for an Endogenous Biogenic Monoamine Mechanism as a Factor in the Impaired Insulin Secretion in Diabetes Mellitus

To investigate the possible role of endogenous catecholamines and serotonin in the impaired insulin release of adult onset diabetes mellitus, intravenous glucose-stimulated insulin secretion was measured in adult onset diabetic patients and in normal volunteers before and during administration of the serotonin blocker methysergide maleate (2 mg every 6 hr for 2 days) or placebo. The increase in insulin secretion as measured by percent change in area under the insulin curve compared to the control study was significantly greater (p < 0.05) during methysergide treatment (48.8 percent) than during placebo administration 5.1 percent) in the diabetic patients. The normal volunteers showed no significant difference in insulin secretion between the methysergide (5.2 percent) and the placebo (10.2 percent). Glucose disappearance constants were unchanged during methysergide administration in most diabetic patients and in the group of normal volunteers. These studies suggest the existence of an endogenous pancreatic biogenic monoamine mechanism which inhibits insulin release in adult onset diabetic patients and could play a role in the pathogenesis of diabetes mellitus.