Effect of adrenalectomy on the development of a pancreatic islet lesion in fa/fa rats

Diabetologia. 1996 Feb;39(2):190-8. doi: 10.1007/BF00403962.

Abstract

Adrenalectomy prevents development of obesity and hyperinsulinaemia in obese (fa/fa) Zucker rats, thereby implicating the hypothalamo- pituitary-adrenal axis in the pathogenesis of obesity. In this study glucose-induced insulin secretion and glucokinase activity were investigated in isolated islets from adrenalectomized and control obese and lean female rats. Islets from control fa/fa rats were more sensitive to glucose with a half-maximal effective concentration (EC50) of 6.1 +/- 2.0 mmol. 1(-1) compared with 10.6 +/- 2.7 mmol. 1(-1) for adrenalectomized fa/fa rat islets. Adrenalectomy did not alter the islet sensitivity to glucose in the lean rats (EC50 of 9.4 +/- 1.5 mmol.1(-1) and 9.3 +/- 2.0 mmol. 1(-1) for adrenalectomized and control lean rats respectively). Mannoheptulose did not inhibit insulin secretion from control obese rats; however at concentrations of 1.0 mmol. 1(-1) or more it significantly inhibited glucose-induced insulin secretion in adrenalectomized obese and lean, and control lean rat islets (P < 0.05). In adrenalectomized fa/fa islets the glucokinase Km was increased twofold compared with the control fa/fa rats (9.5 +/- 1.5 mmol. 1(-1) vs 5.0 +/- 1.5 mmol. 1(-1), respectively), but there was no significant change in glucokinase Km in the lean rat islets after adrenalectomy. Mannoheptulose (10 mmol.1(-1) caused a significant reduction in glucose phosphorylation in disrupted islets of adrenalectomized fa/fa and lean, and of control lean rats, but not of control fa/fa rats. These data demonstrate that development of abnormal regulation of glycolysis in pancreatic islet beta cells of fa/fa rats, as indicated by the insulin response to manno-heptulose and glucokinase activity, is dependent on an intact hypothalamo-pituitary-adrenal axis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenalectomy*
  • Animals
  • Blood Glucose / metabolism
  • Body Weight
  • Cells, Cultured
  • Corticosterone / blood
  • Female
  • Glucokinase / metabolism
  • Glucose / pharmacology
  • Hexokinase / metabolism
  • Hyperinsulinism
  • Insulin / analysis
  • Insulin / metabolism*
  • Insulin Secretion
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / pathology*
  • Islets of Langerhans / physiology*
  • Kinetics
  • Mannoheptulose / pharmacology
  • Obesity / pathology
  • Obesity / physiopathology*
  • Rats
  • Rats, Zucker
  • Thinness

Substances

  • Blood Glucose
  • Insulin
  • Mannoheptulose
  • Hexokinase
  • Glucokinase
  • Glucose
  • Corticosterone