The experiments proposed in this application are an extension of the most significant findings of the investigator's previous project (R29). The investigator found that 5 days of calorie restriction (CR) increased insulin-stimulated glucose transport in young and old rats by 50-100%.
The specific aims of the current application are: 1) to determine if brief CR alters the abundance of insulin receptor substrate (IRS-1) and (IRS-2), and submaximal insulin-stimulated IRS-1 and IRS-2 tyrosine phosphorylation; 2) to determine if brief CR results in increased PI 3K protein and insulin-stimulated IRS-1 and IRS-2 bound activity; 3) to determine the role of insulin-stimulation of PI 3K activity in the CR-induced increase in insulin-stimulated glucose transport; 4) to determine if brief CR leads to a decline in skeletal muscle levels of hexosamines and their precursors; and 5) to gain insight into the processes leading to enhanced insulin action by determining if the rapid acquisition of enhanced glucose transport with brief CR is accompanied by changes in plasma insulin or glucose.
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