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Effects of Caloric Restriction and Growth Hormone Treatment on Insulin-Related Intermediates in The Skeletal Muscle

¹ Physiology, King Saud University, Riyadh, Saudi Arabia
² Physiology & Internal Medicine, SIU School of Medicine, Springfield, IL
³ Division of Diabetes, Endocrinology, and Metabolism, Vanderbilt University School of Medicine, Nashville, TN

ABSTRACT

Reduced IGF-1/insulin signaling and calorie restriction (CR) are known to extend life span and delay age-related diseases. Moreover, these two interventions improves insulin sensitivity in many species. On the other hand, chronic elevation of growth hormone (GH) induces hyperinsulinemia and insulin resistance in both humans and animals. To explore the mechanisms that lead to improved insulin sensitivity in CR animals as well as animals with low levels of GH, and the mechanisms by which GH induces insulin resistance, we subjected normal (N) and growth hormone deficient (Ames) mice to CR for three months with or without daily injections of GH. Protein levels of some signaling molecules involved in insulin activity in skeletal muscle were assessed. Ames muscle has reduced Foxo1 protein levels and GH increased it in these animals. mTOR, a protein that was reported to phosphorylate IRS-1 at a serine residue and cause insulin resistance, was decreased in Ames muscle. GH increased mTOR phosphorylation. GH also increased p38 activation in both N and Ames mice fed ad libitum but not CR. GH also resulted in increased JNK phosphrorylation which is also involved in increased insulin resistance in skeletal muscle. Ames phenotype and GH both resulted in increased CREB phosphrylation.

In conclusion, reduced mTOR and Foxo1 by CR and/or Ames phenotype are very likely to increase insulin sensitivity in these interventions. GH exacerbates insulin resistance in muscle by inducing Foxo1, mTOR, p38, and JNK.

This Article Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Al-Regaiey, K. A Articles by Bartke, A. PubMed Articles by Al-Regaiey, K. A Articles by Bartke, A.