Effects of exercise training on the relationship between insulin binding and insulin-stimulated tyrosine kinase activity in rat skeletal muscle

Abstract

The effect of exercise training on insulin binding and insulin receptor tyrosine kinase activity was studied using detergent solubilized wheat germ agglutinin (WGA)-agarose purified receptor preparations from rat biceps femoris (BF) and tensor fascia lata (TFL) muscles. Insulin receptor activity, as assessed by A14 [ 125I] insulin binding, was significantly elevated in BF of exercise-trained rats when compared with similar preparations from a sedentary control group. This increase in binding activity was due to change in B max not K D. In contrast, neither the B max nor the K D of insulin binding to TFL changed with exercise training. The structure of insulin receptors isolated from BF or TFL was unaltered by exercise training as determined by affinity labeling (α-subunit, molecular weight (mol wt) ∼131 kilodaltons [kDa]) and electrophoretic mobility of the α- and β-subunit. Furthermore, basal tyrosine kinase activity was not affected by exercise training in extracts from either BF or TFL. However, the insulin dependent increase in maximal tyrosine kinase activity (V max) of the BF, but not TFL, was enhanced by exercise training. Specifically, insulin stimulated phosphorylation of both the β-subunit of the insulin receptor (auto phosphorylation) and of a synthetic peptide (exogenous phosphorylation) were increased over control values in BF from exercise-trained rats, whereas both measurements of tyrosine kinase activity of TFL from the two experimental groups were similar. In contrast, both insulin-stimulated autophosphorylation and tyrosine kinase activity were significantly decreased in BF of exercise-trained rats when normalized to insulin binding activity. This disassociation was only seen in BF from exercise-trained rats, and was not true of TFL. These data indicate that excercise training can lead to increases in insulin receptor number and tyrosine kinase activity, as well as modifying the relationship between these two variables. The changes noted are not observed in all exercising muscles, and their development seems to depend upon the fiber composition. These results emphasize the complex relationship that exists in the regulation of insulin action at the level of its receptor.