Effects of Fasting on Insulin Secretion, Islet Glucose Metabolism, and the Cyclic Adenosine 3',5'-Monophosphate Content of Rat Pancreatic Islets In Vitro

Abstract

Fasting for 24 hours inhibits glucose-induced insulin secretion from isolated rat pancreatic islets. At glucose 15 raM the inhibition is only present during the initial 30-45 minutes of stimulation. It decreases at higher glucose concentrations and disappears at glucose 37.5 mM. In islets of fed rats, 15 minutes of stimulation with glucose 15 mM induced an almost threefold rise of islet cyclic adenosine 3',5'-monophosphate (cAMP). Both this effect and the secretory response were inhibited by about 65 per cent after 24 hours of fasting and almost completely by 72 hours of food deprivation. Fasting for 24 hours also caused a 56 per cent inhibition of the rise of islet cAMP and insulin secretion induced by D-glyceraldehyde 10 mM, but the inhibition was not further enhanced by 72 hours of fasting. Fasting for 24 and 72 hours did not significantly inhibit the islet cAMP response to 15 minutes of stimulation with glucose 37.5 mM. Fasting for 24 hours impaired neither islet glucose oxidation (14CO2 production) nor over-all glucose utilization (production of 3H-water from [5-3H] glucose) during the initial 30 minutes of stimulation with glucose. After 72 hours of fasting, both over-all glucose utilization and glucose oxidation were reduced by 25 per cent. These findings suggest that inhibition of the islet cAMP response is a primary factor in the early (24 hours) fasting-induced impairment of the insulin secretory response to glucose stimulation at 5-15 mM. Inhibition of islet glucose metabolism seems to be an independent additional phenomenon that becomes manifest after longer periods of food deprivation.