title: Exogenous insulin enhances glucose-stimulated insulin response in healthy humans independent of changes in free fatty acids.
abstract: BACKGROUND
  Islet β-cells express both insulin receptors and insulin signaling proteins. Recent studies suggest insulin signaling is physiologically important for glucose sensing.
  
  
  OBJECTIVE
  Preexposure to insulin enhances glucose-stimulated insulin secretion (GSIS) in healthy humans. We evaluated whether the effect of insulin to potentiate GSIS is modulated through regulation of free fatty acids (FFA).
  
  
  METHODS
  Subjects were studied on three occasions in this single-site study at an academic institution clinical research center.
  
  
  METHODS
  Subjects included nine healthy volunteers.
  
  
  METHODS
  Glucose-induced insulin response was assessed on three occasions after 4 h saline (low insulin/sham) or isoglycemic-hyperinsulinemic (high insulin) clamps with or without intralipid and heparin infusion, using B28 Asp-insulin that could be distinguished from endogenous insulin immunologically. During the last 80 min of all three clamps, additional glucose was administered to stimulate insulin secretion (GSIS) with glucose concentrations maintained at similar concentrations during all studies.
  
  
  METHODS
  β-Cell response to glucose stimulation was assessed.
  
  
  RESULTS
  Preexposure to exogenous insulin increased the endogenous insulin-secretory response to glucose by 32% compared with sham clamp (P = 0.001). This was accompanied by a drop in FFA during hyperinsulinemic clamp compared with the sham clamp (0.06 ± 0.02 vs. 0.60 ± 0.09 mEq/liter, respectively), which was prevented during the hyperinsulinemic clamp with intralipid/heparin infusion (1.27 ± 0.17 mEq/liter). After preexposure to insulin with intralipid/heparin infusion to maintain FFA concentration, GSIS was 21% higher compared with sham clamp (P < 0.04) and similar to preexposure to insulin without intralipid/heparin (P = 0.2).
  
  
  CONCLUSIONS
  Insulin potentiates glucose-stimulated insulin response independent of FFA concentrations in healthy humans.
authors.affiliation: Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Ximena
authors.initials: X
authors.lastname: Lopez
authors.forename: Aaron
authors.initials: A
authors.lastname: Cypess
authors.forename: Raquel
authors.initials: R
authors.lastname: Manning
authors.forename: Sheila
authors.initials: S
authors.lastname: O'Shea
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; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D016037:Single-Blind Method
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D005947:Glucose