Effect of adrenalectomy on the development of a pancreatic islet lesion in fa/fa rats.
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.
Kibenge
M T
MT
Department of Anatomy and Physiology, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, Canada.
Chan
C B
CB
D000315:Adrenalectomy; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D002478:Cells, Cultured; D003345:Corticosterone / Q000097:blood; D005260:Female; D005941:Glucokinase / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D006593:Hexokinase / Q000378:metabolism; D006946:Hyperinsulinism; D007328:Insulin / Q000032:analysis / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000473:pathology* / Q000502:physiology*; D007700:Kinetics; D008356:Mannoheptulose / Q000494:pharmacology; D009765:Obesity / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D011924:Rats, Zucker; D013851:Thinness
D001786:Blood Glucose; D007328:Insulin; D008356:Mannoheptulose; D006593:Hexokinase; D005941:Glucokinase; D005947:Glucose; D003345:Corticosterone