Evidence for Defective Glucose Sensing by Islets of fa/fa Obese Zucker Rats

Can J Physiol Pharmacol. 1993 Jan;71(1):34-9. doi: 10.1139/y93-005.

Abstract

The hypothesis that a defect in glucose sensing by islets of fa/fa Zucker rats contributes to hyperinsulinemia in these animals was tested. Islets from lean and fa/fa rats were isolated by collagenase digestion and step-density gradient purification and then cultured overnight in Dulbecco's modified Eagle's medium containing 12.5 mM glucose. Obese rat islets were more sensitive to hypoglycemic glucose levels with half-maximal effective concentration (EC50) of 5.6 mM compared with an EC50 of 8.2 mM for lean rat islets. In contrast, responsiveness of both phenotypes to alpha-ketoisocaproate and quinine was similar. Mannoheptulose did not inhibit insulin secretion from fa/fa islets, although inhibitors of later events in the stimulus-secretion coupling pathway were normally inhibited by iodoacetate and diazoxide. Finally, starvation in vivo and culture of islets in low glucose concentrations (5 mM) in vitro both decreased glucose-stimulated insulin secretion from lean but not fa/fa rat islets. We conclude that fa/fa rat islets have an exaggerated insulin response to hypoglycemic stimuli, possibly as a result of a defect in B-cell glucokinase function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / pharmacology
  • Amino Acids / pharmacology
  • Animals
  • Blood Glucose / metabolism
  • Diazoxide / pharmacology
  • Female
  • Glucokinase / antagonists & inhibitors
  • Glucose / metabolism*
  • Insulin / metabolism
  • Insulin Secretion
  • Iodoacetates / pharmacology
  • Iodoacetic Acid
  • Islets of Langerhans / metabolism*
  • Mannoheptulose / pharmacology
  • Obesity / metabolism*
  • Organ Culture Techniques
  • Quinine / pharmacology
  • Rats
  • Rats, Zucker
  • Starvation / metabolism

Substances

  • Amino Acids
  • Blood Glucose
  • Insulin
  • Iodoacetates
  • Mannoheptulose
  • Adenosine Triphosphate
  • Quinine
  • Glucokinase
  • Glucose
  • Diazoxide
  • Iodoacetic Acid