Effects of Aging and Experimentally Induced Modifications of Signal Pathways on Insulin-Induced Shifts of Glucose Metabolism in the Rat Neocortex

Abstract

We studied insulin-induced intensification of glucose absorption and glycogen formation in the neocortex of young and old rats. In young animals, the corresponding shifts were clearly expressed; in old rats, insulin exerted nearly no stimulatory action on the processes of glucose metabolism in neocortical tissues. It was hypothesized that this is due to the age-related enhancement of the level of ceramides resulting in changes of the lipid spectrum of the cell membranes and also due to suppression of key components of signal pathways of insulin in the brain (such as Akt/protein kinase В, ARF, protein kinase С, and phospholipase D). These events disturb the signal cascade of the hormone and process of formation of the physiological response. An increase in the amount of ceramides in neocortical tissues of young animals after the action of exogenous С2 ceramide or palmitic acid (precursor of sphingolipids) was accompanied by suppression of the intensification of glucose absorption and insulin-stimulated formation of glycogen. Taking into account a significant increase in the amount of ceramides in the neocortex of old animals (this was shown in our earlier study), we believe that age-related accumulation of ceramide is an important reason for the development of insulin resistance of glucose metabolism in the CNS of old organisms.