STIMULUS-SECRETION COUPLING AND INSULIN-SECRETION IN AGING - EVALUATION OF GLUCOSE-OXIDATION AND ATP-SENSITIVE POTASSIUM CHANNEL RESPONSIVENESS

The purpose of this study was to evaluate possible age-related alterat ions in the glucose-stimulus/insulin-secretion coupling mechanism of i slets of Langerhans. To this end, the interaction among insulin secret ion, glucose oxidation, and ATP-sensitive potassium (K-ATP) channel re sponsiveness was determined in islets of Langerhans isolated from 6-, 12-, and 26-month-old male Fischer 344 (F344) rats. Groups of 20 islet s 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 mu M glyburide and either 1.7 or 11.1 mM glucose; (3) 5 mu M epinephrine and 11.1 mM glucose; or (4 ) 1.2. mu M glyburide, 5 mu M epinephrine, and either 1.7 or 11.1 mM g lucose. Insulin release of islets incubated in the presence of glyburi de and 1.7 or 11.1 mM glucose was greater than that of islets incubate d in glucose alone, while glucose oxidation did not increase. Epinephr ine 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. Thes e results indicate that if age-related alterations are occurring in gl ucose-stimulus/insulin-secretion coupling, then such alterations are n ot associated with changes in K-ATP channel-mediated responsiveness.