Developmental Expression of Receptors for Insulin, Insulin-like Growth Factor I (IGF-I), and IGF-II in Rat Skeletal Muscle*

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Abstract
Insulin and insulin-like growth factors (IGFs) stimulate responses in skeletal muscle that include effects on carbohydrate and fat metabolism, protein turnover, growth, and differentiation. To gain insight into the relative importance of insulin and IGFs at different stages of development, the expression of their specific receptors was evaluated in skeletal muscle of rats from the late fetal period through 40 weeks of age. Distinct receptors for insulin. IGF-1, and IGF-II are present in crude membrane preparations and wheat germ agglutinin-purified extracts of hindlimb muscle from rats at all ages, but each of the three receptors follows a different pattern of expression during development. There is a marked predominance of IGF-II receptors in fetal muscle (80- and 55-fold more abundant than insulin and IGF-I receptors, respectively) and a rapid decline in IGF-II receptors in early postnatal life. IGF-1 receptors are more abundant than insulin receptors in the term fetus, remain constant in number until approximately 4 weeks of age, and then gradually decline to adult levels. Insulin receptor number rises 2- to 3-fold postnatally, peaks at approximately 4 weeks, and decrease to levels in the adult that are slightly lower than those in the term fetus. Although binding affinities and receptor specificity did not change during development, the relatively large number of IGF-II receptors in the fetus resulted in significant binding to IGF-1 to receptors for both IGF-II and IGF-I. There was a modest increase in apparent mol wt of all three receptor types during development, suggesting a change in a common pathway, such as posttranslational glycosylation. The marked changes in number and distinct patterns of expression of the insulin, IGF-I, and IGF-II receptors in muscle during development are consistent with evolving functions of the three hormone determined by alterations in both receptor number and hormones concentrations.

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