Beta-cell hypersensitivity to glucose following 24-h exposure of rat islets to fatty acids

Diabetologia. 1997 Apr;40(4):392-7. doi: 10.1007/s001250050692.

Abstract

Prolonged exposure of islets to fatty acids results in a lowered glucose set-point for insulin secretion. We examined the mechanism in islets cultured for 24 h with 0.25 mmol/l palmitate. As expected, insulin secretion at 2.8 and 8.3 mmol/l glucose was increased in the palmitate-treated islets as opposed to no change at 27.7 mmol/l glucose. Co-culturing with 0.05 microgram/ml Triacsin C, an inhibitor of long chain acyl-CoA synthetase, blocked this effect. Glucose utilization and oxidation showed the same pattern as insulin secretion, with the step-up for both measurements being fully manifest at 2.8 mmol/l glucose. Glucokinase Km and Vmax measured in islet extracts were unaffected by the palmitate. In contrast, hexokinase Vmax was increased by 25-35% in both the cytoplasmic and mitochondrial-bound pools. Our data suggest prolonged exposure to fatty acids increased beta-cell hexokinase activity, thereby modifying the kinetics of glucose entry into the metabolic pathway and glucose-induced insulin secretion. The cellular mediator is likely an increased level of long chain fatty acyl-CoA esters.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cells, Cultured
  • Coculture Techniques
  • Coenzyme A Ligases / antagonists & inhibitors
  • Cytoplasm / metabolism
  • Enzyme Inhibitors / pharmacology
  • Glucokinase / metabolism
  • Glucose / metabolism*
  • Glucose / pharmacology*
  • Glycolysis / drug effects
  • Hexokinase / metabolism
  • Insulin / metabolism*
  • Insulin Secretion
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / physiology*
  • Kinetics
  • Male
  • Mitochondria / metabolism
  • Palmitic Acid / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Triazenes / pharmacology*

Substances

  • Enzyme Inhibitors
  • Insulin
  • Triazenes
  • Palmitic Acid
  • triacsin C
  • Hexokinase
  • Glucokinase
  • Coenzyme A Ligases
  • Glucose