Consumption of a Glucose Diet Enhances the Sensitivity of Pancreatic Islets from Adrenalectomized Genetically Obese (ob/ob) Mice to Glucose-Induced Insulin Secretion

Abstract

Consumption of a glucose diet for 4 d markedly elevates plasma insulin concentrations in adrenalectomized ob/ob mice. The present study examined 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 commercial 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, pancreatic islet size, rates of insulin secretion in response to 20 mmol/L glucose and insulin mRNA relative abundance in ob/ob and lean mice fed the commercial diet, but the threshold for glucose-induced insulin secretion determined by a linear glucose gradient remained lower in islets 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 glucose 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 increased plasma insulin concentrations ∼10-fold in islets from adrenalectomized ob/ob mice without affecting islet size, 20 mmol/L glucose-induced insulin secretion or insulin mRNA abundance. Consumption 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 insulin secretion seems to be persistently altered in ob/ob mice.