INSULIN-SENSITIVE TYROSINE KINASE-ACTIVITY CHANGES IN PARALLEL WITH PLASMA-INSULIN AND GLUCOSE-CONCENTRATIONS IN HUMANS

Insulin receptor tyrosine kinase is an important step in insulin action. We examined the relationship between diet-induced changes in glucose metabolism and changes in skeletal muscle insulin-sensitive tyrosine kinase activity in 12 nondiabetic subjects. Subjects were fed a traditional, high carbohydrate Pima Indian diet and a modern, high fat western diet for 2 weeks in a randomized cross-over design. At the end of each dietary period, glucose tolerance was assessed, insulin sensitivity (S(I)) was estimated by Bergman's minimal model method, and insulin receptor concentration and tyrosine kinase activity were determined on lectin-purified extracts from quadriceps femoris muscle. Compared to the traditional diet, the modern diet was associated with a deterioration of glucose tolerance and an increase in glucose-induced plasma insulin levels. As expected, S(I) changes were associated with opposite changes in plasma insulin levels. However, the changes in maximal tyrosine kinase activity were negatively correlated with changes in S(I) (r = -0.69; P < 0.01) and positively correlated with changes in plasma glucose (r = 0.70; P < 0.01) and insulin response to glucose (r = 0.57; P < 0.025). These results suggest that the site of diet-induced changes in insulin action is beyond the insulin-sensitive tyrosine kinase. The results further suggest that the kinase activity is modulated by prevailing plasma insulin levels.