EFFECTS OF AGE, DIET AND OBESITY ON INSULIN-SECRETION FROM ISOLATED-PERFUSED RAT PANCREAS - RESPONSE TO GLUCOSE, ARGININE AND GLUCAGON-LIKEPEPTIDE-1 (7-37)

The insulin secretory responses to glucose, arginine and glucagon-like peptide (GLP)-1-(7- 37 have been evaluated from the isolated perfused pancreas of rats with either acquired or genetic obesity, ie, a) fed ad libitum 14-mo old Sprague-Dawley rats as compared to age-matched an imals subjected to two types of dietary restriction (every-other-day f eeding, EOD, and 40% restriction? 40% DR), and b) 2.5-mo old genetical ly obese fa/fa rats as compared to the lean counterpart, In mature fed ad libitum rats, the glucose-stimulated insulin release from the perf used pancreas was increased 5-fold by addition of 0.1 nM GLP-1 (7-37), a subsequent challenge with high glucose resulted in an improvement o f the first phase of insulin release, In 40% DR rats, a similar patter n of secretion was observed, with the difference of a lower response t o arginine than in fed ad libitum animals, In EOD rats, the overall se cretory performance of the perfused pancreas was approximately 50% low er than in the fed ad libitum group but probably adequate to the reduc ed weight of the animals, In genetically obese young rats, both the re sponse to GLP-1 (7-37) anti the total insulin secretion were higher th an in the lean controls. Interestingly, the maximal insulin outputs fr om the perfused pancreases were observed in both the groups of overwei ght animals, In conclusion no impairment in the secretory responsivene ss of beta-cells occurs in obese animals, Conversely, at least within the age limits of the present study, the endocrine pancreas develops a compensatory ability to match the augmented insulin demand due to the over-weight. In the light of the observed great sensitivity of the is olated perfused pancreas to GLP-1 (7-37), changes in the responsivenes s of beta-cells to incretins might be involved in the modulation of th e endocrine pancreatic function of obese rats.