Age-dependent reduction in GLUT-2 levels is correlated with the impairmentof the insulin secretory response in isolated islets of Sprague-Dawley rats

In this study we have investigated the insulin secretory response to glucos e and other secretagogues (2-ketoisocaproate, 3-isobutyl-1-methyl-xanthine and arginine) of pancreatic islets isolated from Sprague-Dawley rats of var ious ages (from 2 to 28 months). Our results showed a significant decline i n the glucose-stimulated insulin secretion, starting at 12 months of age. O n the other hand, the response to non-glucose secretagogues (and mainly to 2-ketoisocaproate) was less impaired with advancing age than that to glucos e. We also observed a progressive age-related decline of protein levels of the glucose transporter GLUT-2 in pancreatic islets, which was temporally c oncomitant and quantitatively comparable with the beta-cell alteration in g lucose responsiveness (-40/50%). Finally, we observed a significant increas e of the islets insulin content in older rats with respect to younger anima ls. We conclude that in the islet of older rats the impaired capability to respond to glucose could be dependent, at least in part, on the age-depende nt reduction in GLUT-2 and could be compensated by mechanisms including a p reserved responsiveness to non-glucose secretagogues and/or the development of islet hypertrophy. (C) 2000 Elsevier Science Inc. All lights reserved.