Fast Insulin Secretion Blunted by Impaired Insulin Storage of Islet ß Cells in Mice

Purpose: To clarify the effects of cellular insulin content and restoration on fast insulin secretion after acute hyperglycemia challenges. Methods: To analyze the impairment and recovery mechanisms of acute hyperglycemia on the first phase insulin secretion, we evaluated the function of insulin secretion by glucose tolerance test. To explore the ramification of insulin secretion and storage in pancreatic islets after acute hyperglycemia challenges, we isolated the islet for GSIS and measured insulin content in vitro. HE for pancreas tissues were performed to study morphologic changes of the islets and to assess the impact of acute hyperglycemia on islet histology. EM for β cells were used to study morphologic changes of insulin granules. Results: The mice with acute hyperglycemia showed, (1) blunted early insulin secretion in impaired glucose tolerance test; (2) disrupted insulin secretion using static islet incubation at low (2.8 mmol/l), high (16.7 mmol/l) glucose, 30 or 40mmol/l Potassium Chloride stimulus; (3) lack of intracellular insulin content. Five days after termination of hyperglycemic treatment, blunted early insulin secretion and glucose levels were completely reversed in the glucose tolerance test, but insulin contents in islet study did not return to the values of the control groups. In morphological study, irregular islets in HE and decreased insulin granules in EM caused by hyperglycemia did not alleviate. Conclusions: Blunted fast insulin secretion and impaired glucose tolerance caused by acute intravenous hyperglycemia can be reversed, but poor insulin storage remained.