Reaven G. Effect of age and environmental factors on insulin release from the perfused pancreas of the rat

age and various age-related environmental factors on maximal glucose-stimulated insulin release by the in-tact perfused pancreas. Male Sprague-Dawley rats were maintained from 40 d to 12 mo of age on standard chow, or on a sucrose-rich or calorie-restricted diet. At 12 mo, studies were carried out on the isolated pancreas of each animal to determine maximal (300 mg/ml) glucose-stimulated insulin secretion. After these studies were completed, each pancreas was per-fused with formalin fixative and processed for mor-phometric estimation of the mass of the endocrine pancreas. Data from these older animals were com-pared with data from 2-mo-old control rats. The results indicate that maximal glucose-stimulated insulin se-cretion per unit endocrine pancreas was markedly re-duced in all three groups of 12-mo-old rats, and was only 25-33 % of that of 2-mo-old rats. Thus, aging led to a decline in insulin secretion per beta cell that was not modifiable by environmental manipulation. On the other hand, environmental factors can influence the development of endocrine tissue within the pancreas, and in so doing, modify total pancreatic insulin secre-tion. The mass of the endocrine pancreas of 12-mo-old rats fed either sucrose or chow was between three and four times that of 2-mo-old control rats, and these older rats were able to maximally secrete as much insulin per total pancreas as the young rats. In contrast, the endocrine cell mass of the calorie-restricted rats had not enlarged to this extent, and the maximally stim-ulated perfused pancreas from these rats secreted less insulin. These data suggest that the aging animal, chal-lenged in vivo to secrete insulin, can overcome the loss of the beta cell response by expanding its pancreatic Address all correspondence to Dr. E. Reaven. Received for publication 17 May 1982 and in revisedfor