Summary
Adrenalectomy prevents development of obesity and hyperinsulinaemia in obese (fa/fa) Zucker rats, thereby implicating the hypothalamopituitary-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 · l−1 compared with 10.6±2.7 mmol · l−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 · l−1 and 9.3±2.0 mmol · l−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 · l−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 · l−1 vs 5.0±1.5 mmol · l−1, respectively), but there was no significant change in glucokinase Km in the lean rat islets after adrenalectomy. Mannoheptulose (10 mmol · l−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 mannoheptulose and glucokinase activity, is dependent on an intact hypothalamo-pituitary-adrenal axis.
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Abbreviations
- ADX:
-
Adrenalectomy/adrenalectomized
- CRH:
-
corticotrophin releasing hormone
- DMEM:
-
Dulbecco's modified Eagle's medium
- EC50 :
-
half-maximal effective concentration
- HPA:
-
hypothalamo-pituitary-adrenal
- MH:
-
mannoheptulose
- Hepes:
-
4-(2-hydroxyethyl)-1-piperazineethane sulphonic acid
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Kibenge, M.T., Chan, C.B. Effect of adrenalectomy on the development of a pancreatic islet lesion in fa/fa rats. Diabetologia 39, 190–198 (1996). https://doi.org/10.1007/BF00403962
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DOI: https://doi.org/10.1007/BF00403962