Lack of suppression of insulin secretion by hyperinsulinemia in a patient with an insulinoma

The regulation of insulin secretion in patientswith insulinoma is known to be abnormal. For example, physiologicaland pharmacological stimuli often fail to stimulateinsulin in such patients. Recently, insulin has been found toinhibit its own secretion in normal subjects. To determine ifinsulin has this effect in patients with insulinoma, we infusedinsulin at rates of 1 and 10 mU/kg-min in such a patient and ineight normal subjects. Euglycemia was maintained by the euglycemicglucose clamp technique, and endogenous insulin secretionwas estimated by measuring plasma C-peptide levels. In thenormal subjects, plasma C-peptide declined from 1.60 ± 0.22 (±SEM) to 1.16 ± 0.17 and 0.82 ± 0.11 ng/ml during the low and high dose insulin infusions, respectively, indicating 27% (P <0.01) and 48% (P < 0.001) decreases in endogenous insulinsecretion at moderately elevated and extremely elevated insulinlevels, respectively. In the insulinoma patient, plasma C-peptidewas 2.6 ng/ml basally, did not change during the low dose insulininfusion, and rose to 3.4 ng/ml during the high dose insulininfusion.We conclude that the feedback regulation of insulin secretionby insulin that occurs in normal subjects is absent in insulinomapatients. This finding could have pathophysiological and possiblydiagnostic significance.