CONSUMPTION OF A GLUCOSE DIET ENHANCES THE SENSITIVITY OF PANCREATIC-ISLETS FROM ADRENALECTOMIZED GENETICALLY-OBESE (OB OB) MICE TO GLUCOSE-INDUCED INSULIN-SECRETION/

Consumption of a glucose diet for 4 d markedly elevates plasma insulin concentrations in adrenalectomized ob/ob mice. The present study exam ined regulation of insulin secretion from perifused pancreatic islets of female adrenalectomized genetically obese (ob/ob) and lean mice fed a glucose diet for 4 d. These mice were fed a high carbohydrate comme rcial diet for 21 d, or the high carbohydrate commercial diet for 17 d and a purified high glucose diet for the last 4 d of the 21-d feeding period. Adrenalectomy equalized plasma insulin concentrations, pancre atic islet size, rates of insulin secretion in response to 20 mmol/L g lucose and insulin mRNA relative abundance in ob/ob and lean mice fed the commercial diet, but the threshold for glucose-induced insulin sec retion determined by a linear glucose gradient remained lower in islet s from adrenalectomized ob/ob mice than in those from lean mice (3.8 /- 0.1 vs. 4.9 +/- 0.2 mmol/L glucose), and addition of acetylcholine to the perifusate lowered the threshold to only 2.0 +/- 0.1 mmol/L glu cose in islets from ob/ob mice vs. 3.3 +/- 0.1 mmol/L glucose in lean mice. Switching from the commercial diet to the glucose diet for 4 d i ncreased plasma insulin concentrations similar to 10-fold in islets fr om adrenalectomized ob/ob mice without affecting islet size, 20 mmol/L glucose-induced insulin secretion or insulin mRNA abundance. Consumpt ion of the glucose diet did, however, markedly lower the threshold for glucose-induced insulin secretion in islets from adrenalectomized ob/ ob mice to approximate the abnormally low glucose thresholds in intact ob/ob mice. Islets from lean mice were unaffected by the diet switch. The signaling pathway that sensitizes islets to glucose-induced insul in secretion seems to be persistently altered in ob/ob mice.