Hyperinsulinaemia and insulin insensitivity: studies in subjects with insulinoma.
Hepatic glucose turnover, peripheral insulin sensitivity and insulin receptor binding were measured in four subjects with insulinoma before and 3 months after surgical resection of the insulinoma. Basal hepatic glucose production, quantitated employing a primed constant infusion of tritiated glucose, was low pre-operatively (5.2 +/- 1.7 mumol X kg-1 X min-1) but returned to normal post-operatively (14.9 +/- 2.8; normal subjects 13.9 +/- 0.8 mumol X kg-1 X min-1). Paired euglycaemic dose-response curves were developed for each subject. Insulin sensitivity, expressed as a right shift of the dose-response curve (ED50), was low pre- and post-operatively. However, insulin responsiveness (Vmax) remained normal (pre-operatively 13.9 +/- 2.2, post-operatively 13.8 +/- 0.8, normal subjects 16.7 +/- 0.8 ml X kg-1 X min-1). There was no consistent pattern in monocyte or erythrocyte receptor binding before or after surgery. These data suggest that the chronic hyperinsulinaemia causes suppression of hepatic glucose production, and a state of insulin insensitivity which appears to be due to a post-receptor defect.
D007516:Adenoma, Islet Cell / Q000378:metabolism*; D000368:Aged; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D007340:Insulinoma / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D011972:Receptor, Insulin / Q000378:metabolism
D007328:Insulin; D011972:Receptor, Insulin; D005947:Glucose