title: Insulin enhances glucose-stimulated insulin secretion in healthy humans.
abstract: Islet beta-cells express both insulin receptors and insulin-signaling proteins. Recent evidence from rodents in vivo and from islets isolated from rodents or humans suggests that the insulin signaling pathway is physiologically important for glucose sensing. We evaluated whether insulin regulates beta-cell function in healthy humans in vivo. Glucose-induced insulin secretion was assessed in healthy humans following 4-h saline (low insulin/sham clamp) or isoglycemic-hyperinsulinemic (high insulin) clamps using B28-Asp insulin that could be immunologically distinguished from endogenous insulin. Insulin and C-peptide clearance were evaluated to understand the impact of hyperinsulinemia on estimates of beta-cell function. Preexposure to exogenous insulin increased the endogenous insulin secretory response to glucose by approximately 40%. C-peptide response also increased, although not to the level predicted by insulin. Insulin clearance was not saturated at hyperinsulinemia, but metabolic clearance of C-peptide, assessed by infusion of stable isotope-labeled C-peptide, increased modestly during hyperinsulinemic clamp. These studies demonstrate that insulin potentiates glucose-stimulated insulin secretion in vivo in healthy humans. In addition, hyperinsulinemia increases C-peptide clearance, which may lead to modest underestimation of beta-cell secretory response when using these methods during prolonged dynamic testing.
authors.affiliation: Cellular and Molecular Physiology, Joslin Diabetes Center, Boston, MA 02215, USA.
authors.forename: Clara
authors.initials: C
authors.lastname: Bouche
authors.forename: Ximena
authors.initials: X
authors.lastname: Lopez
authors.forename: Amy
authors.initials: A
authors.lastname: Fleischman
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Cypess
authors.forename: Sheila
authors.initials: S
authors.lastname: O'Shea
authors.forename: Darko
authors.initials: D
authors.lastname: Stefanovski
authors.forename: Richard N
authors.initials: RN
authors.lastname: Bergman
authors.forename: Eduard
authors.initials: E
authors.lastname: Rogatsky
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Stein
authors.forename: C Ronald
authors.initials: CR
authors.lastname: Kahn
authors.forename: Rohit N
authors.initials: RN
authors.lastname: Kulkarni
authors.forename: Allison B
authors.initials: AB
authors.lastname: Goldfine
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000378:metabolism / Q000493:pharmacokinetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D006728:Hormones / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D016037:Single-Blind Method; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D006728:Hormones; D007004:Hypoglycemic Agents; D007328:Insulin; D005947:Glucose