title: Metabolic consequences of prolonged hyperinsulinemia in humans. Evidence for induction of insulin insensitivity.
abstract: Hyperinsulinemia is frequently associated with a variety of insulin-resistant states and has been implicated causally in the development of insulin resistance. This study examines the metabolic consequences of prolonged hyperinsulinemia in humans. Basally and 1 h after cessation of a 20-h infusion of insulin (0.5 mU X kg-1 X min-1, aimed at elevating plasma insulin levels to approximately 30 mU/L) or normal saline, subjects were assessed for glucose turnover with 3-[3H]glucose; insulin sensitivity, as measured by either the euglycemic glucose-clamp technique or the intravenous glucose tolerance test (IVGTT) minimal model method of Bergman; and monocyte insulin-receptor binding. Hepatic glucose production (Ra) was suppressed by greater than 95% during each euglycemic clamp and during the 20-h insulin infusion. After the insulin infusion, Ra and glucose utilization rate returned to the initial basal level within 1 h, as did insulin levels. At that time, insulin sensitivity was significantly decreased, as measured by the "insulin action" parameter during the 40- to 80-min phase of the clamp (0.049 +/- 0.003 vs. 0.035 +/- 0.007 min-1, P less than .05) and during the 80- to 120-min phase (0.047 +/- 0.005 vs. 0.039 +/- 0.007 min-1, .05 less than P less than .1).(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000328:Adult; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D009000:Monocytes / Q000378:metabolism; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007328:Insulin; D011972:Receptor, Insulin; D005947:Glucose