Stimulus-secretion coupling and insulin secretion in aging: evaluation of glucose oxidation and ATP-sensitive...

The purpose of this study was to evaluate possible age-related alterations in the glucose-stimulus/insulin-secretion coupling mechanism of islets of Langerhans. To this end, the interaction among insulin secretion, glucose oxidation, and ATP-sensitive potassium (K ATP) channel responsiveness was determined in islets of Langerhans isolated from 6-, 12-, and 26-month-old male Fischer 344 (F344) rats. Groups of 20 islets were incubated for 40 min at 37 degrees C in a buffer containing: (1) either 1.7 or 11.1 mM glucose; (2) 1.2 microM glyburide and either 1.7 or 11.1 mM glucose; (3) 5 microM epinephrine and 11.1 mM glucose; or (4) 1.2 microM glyburide, 5 microM epinephrine, and either 1.7 or 11.1 mM glucose. Insulin release of islets incubated in the presence of glyburide and 1.7 or 11.1 mM glucose was greater than that of islets incubated in glucose alone, while glucose oxidation did not increase. Epinephrine inhibited insulin release and glucose oxidation at 11.1 mM glucose and abolished glyburide-enhanced insulin release at 11.1 mM glucose. No effect of age was observed in any of the treatment categories. These results indicate that if age-related alterations are occurring in glucose-stimulus/insulin-secretion coupling, then such alterations are not associated with changes in K ATP channel-mediated responsiveness.