title: Metabolic effects of hypoglycemic counterregulation during sustained mild hyperinsulinemia and constant glucose availability in healthy men.
abstract: Posthypoglycemic metabolic changes have been studied predominantly during waning of insulin action. We evaluated the effects of hypoglycemic counterregulation on glucose and lipid metabolism during continuous insulin infusion. Glucose was infused at a constant rate throughout the study (4 mg.kg-1.min-1). During the second part of the study, plasma glucose levels were clamped at approximately 4 mM by variable insulin infusion. In six subjects, but not in five control subjects, short-term hypoglycemia (nadir plasma glucose 2.80 +/- 0.05 mM) was induced by an additional bolus injection of insulin before starting insulin infusion. Substrate oxidation rates and plasma substrate fluxes were determined by indirect calorimetry and primed continuous infusions of [3-3H]glucose and [14C]palmitate. After hypoglycemia, higher insulin infusion rates than in the control group were required to clamp plasma glucose concentrations at similar levels (p < 0.05). Additionally, insulin levels were increased compared with those in control subjects (p < 0.01). There were no differences in substrate oxidation rates, hepatic glucose production, or lipolysis after hypoglycemia. In conclusion, the counterregulatory hormonal response after short-lasting mild hypoglycemia with sustained modest hyperinsulinemia and constant glucose availability induces insulin resistance with respect to glucose uptake but is unable to stimulate hepatic glucose production or lipolysis.
authors.affiliation: Department of Internal Medicine, University of Amsterdam, The Netherlands.
authors.forename: M H
authors.initials: MH
authors.lastname: Godfried
authors.forename: J A
authors.initials: JA
authors.lastname: Romijn
authors.forename: E
authors.initials: E
authors.lastname: Endert
authors.forename: H P
authors.initials: HP
authors.lastname: Sauerwein
mesh_terms: D000328:Adult; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism*; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000378:metabolism*; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000097:blood*; D007333:Insulin Resistance; D007657:Ketone Bodies / Q000097:blood; D050356:Lipid Metabolism; D008066:Lipolysis; D008099:Liver / Q000378:metabolism; D008297:Male; D014280:Triglycerides / Q000097:blood
chemical_list: D005230:Fatty Acids, Nonesterified; D007328:Insulin; D007657:Ketone Bodies; D014280:Triglycerides; D005947:Glucose