The role of vitamin D in muscle metabolism and insulin signaling

Catherine Marie Pinkston, Purdue University

Abstract

There is strong agreement in the literature that vitamin D may be beneficial for muscle function and insulin resistance. Epidemiological evidence suggests that individuals with higher serum 25-dihydroxyvitamin D (25OHD) levels have a decreased risk for falls and muscle weakness as well as insulin resistance and diabetes. In addition, a previous animal study has shown that rats fed a diet high in dairy (high vitamin D, high calcium, and whey protein) had greater lean mass as well as higher insulin receptor (IR) gene expression in muscle. The purpose of the current work was to investigate potential mechanisms, both in vitro and in vivo, whereby vitamin D may exert its beneficial effects in muscle. Consistent with the existing literature, the current animal study confirmed that diets high in either vitamin D, calcium or both result in an approximate 10% increase in lean mass compared to animals fed suboptimal vitamin D and calcium levels. Although there was no change in gene expression of several insulin signaling proteins in muscle including IR, there was significantly higher expression of adiponectin in adipose, a protein which has been implicated in improving insulin sensitivity. To better understand a mechanism for the observations made in the animal study, the differentiated C2C12 myocyte cell model was used. After 72 hour co-treatment with insulin and 1, 25-dihydroxyvitamin D (1,25(OH)2D), there was a significant increase in myotube hypertrophy and AKT activation, suggesting increased insulin signaling. In addition, 1,25(OH)2D alone increases IR gene expression. Finally, treatment with 1,25(OH)2D both alone and when combined with insulin, significantly increased activation of a key regulator in protein synthesis, mammalian target of rapamycin (mTOR), suggesting that 1,25(OH)2D can induce the protein synthetic pathway, a possible mechanism by which vitamin D could induce muscle hypertrophy. Thus, the results of the current studies support that vitamin D is essential in maintaining healthy, insulin sensitive muscle.

Degree

M.S.

Advisors

Teegarden, Purdue University.

Subject Area

Nutrition

COinS