AGE-RELATED-CHANGES IN PANCREATIC-ISLET CELL GENE-EXPRESSION

Previous studies have indicated that insulin secretion in response to glucose diminishes with age but insulin synthesis and gene transcripti on do not. To determine whether expression of genes other than those t hat encode insulin are subject to age related changes that could alter pancreatic islet function, mRNAs for insulins I and II, amylin, gluco se transporter 2 (GluT2), glucagon, and glucokinase were quantified in 2-, 6-, 12-, and 24-month-old Fischer 344 rats using species-specific ribonuclease (RNase) protection assays. There was only a modest (1.2- to 1.3-fold) increase in insulin I and insulin II mRNAs between ages 2 and 12 months. There were no statistically significant changes in le vels of glucokinase mRNA with age. In contrast, the abundances of amyl in, GluT2, and glucagon mRNAs all doubled during the same period. Vari ance in values from 24-month-old rats was too great to allow conclusio ns, except that the ratio of insulin II mRNA to insulin I mRNA increas ed with age. This change was not related to islet mass or total insuli n mRNA abundance because it persisted at age 24 months, when total mRN A abundance had decreased. These results indicate that aging is associ ated with significant alterations in the relative proportion of expres sion of pancreatic islet cell genes implicated in insulin secretion an d in intraislet glucose metabolism.