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Effects of Caloric Restriction and Growth Hormone Resistance on Insulin-Related Intermediates in the Skeletal Muscle

Departments of ¹ Internal Medicine, ² Physiology, ³ Pharmacology, and ⁴ Microbiology and Molecular Biology, Southern Illinois University, School of Medicine, Springfield.
⁵ Edison Biotechnology Institute, Ohio University College of Osteopathic Medicine, Athens.

Address correspondence to Khalid A. Al-Regaiey, DVM, PhD, Department of Physiology, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia. E-mail: kalregai{at}gmail.com

Growth hormone receptor-deficient (GHRKO) mice are long-lived and have reduced insulin-like growth factor (IGF)-1 and insulin levels and enhanced insulin sensitivity thus resembling the phenotype of animals subjected to calorie restriction (CR). In contrast to its effects in normal mice, CR does not improve insulin sensitivity or increase longevity in GHRKO males. In an attempt to identify mechanisms underlying this differential response to CR, effects of CR on the expression of insulin-related genes were compared in GHRKO and normal mice. In addition to changes detected in both genotypes, and responses unique to GHRKO mice, the levels of Akt2 and peroxisome proliferator-activated receptor- coactivator-1 (PGC1) were increased and levels of phosphorylated c-Jun N-terminal kinase (JNK)1 were reduced in response to CR only in normal mice. These changes may be related to mechanisms of improving insulin sensitivity and life expectancy.

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