Vitamin D deficiency aggravates diabetes-induced muscle wasting in female mice
- 160 Downloads
We recently reported that vitamin D deficiency aggravates diabetic bone loss in mice. Although vitamin D affects both muscle and bone, the role of the vitamin D state in diabetic muscle loss and muscle-bone relationships remains unclear. In the present study, we examined the effects of vitamin D deficiency on muscle mass, muscle differentiation and muscle-derived humoral factors linking muscle to bone in diabetic female mice. Diabetes was induced in mice by streptozotocin (STZ) injection after feeding with a normal or vitamin D-deficient diet for 6 weeks. Quantitative computed tomography analysis showed that tibial muscle mass was significantly decreased in diabetic mice compared with control mice 4 weeks after induction of diabetes. Vitamin D deficiency accelerated muscle loss in diabetic mice. Vitamin D deficiency augmented the decreases in Pax7 mRNA levels and the increases in muscle RING-Finger Protein-1 and atrogin-1 mRNA levels induced by diabetes in the gastrocnemius muscle of mice. Moreover, vitamin D deficiency decreased the mRNA levels of insulin-like growth factor-1, fibroblast growth factor-2 and osteoglycin in muscle of diabetic mice. In conclusion, we demonstrated that vitamin D deficiency aggravates muscle loss induced by diabetes in female mice. Vitamin D may exert significant effects on the maintenance of the musculoskeletal system partly through the muscle-bone relationships in diabetic state.
KeywordsVitamin D Diabetes Muscle wasting Myoblast
This study was supported by Grants-in-aid 26860152 and 15K08220 from the Ministry of Science, Education and Culture of Japan (to Y.T. and to H.K., respectively) and a grant from The Nakatomi Foundation.
Compliance with ethical standards
Conflict of interest
All institutional and national guidelines for the care and use of laboratory animals were followed.
- 17.Beaudart C, Buckinx F, Rabenda V, Gillain S, Cavalier E, Slomian J, et al. The effects of vitamin D on skeletal muscle strength, muscle mass, and muscle power: a systematic review and meta-analysis of randomized controlled trials. J Clin Endocrinol Metab. 2014;99:4336–45.CrossRefPubMedGoogle Scholar
- 26.Garcia LA, King KK, Ferrini MG, Norris KC, Artaza JN. 1,25(OH)2vitamin D3 stimulates myogenic differentiation by inhibiting cell proliferation and modulating the expression of promyogenic growth factors and myostatin in C2C12 skeletal muscle cells. Endocrinology. 2011;152:2976–86.CrossRefPubMedPubMedCentralGoogle Scholar
- 34.Lambertucci AC, Lambertucci RH, Hirabara SM, Curi R, Moriscot AS, Alba-Loureiro TC, et al. Glutamine supplementation stimulates protein-synthetic and inhibits protein-degradative signaling pathways in skeletal muscle of diabetic rats. PLoS ONE. 2012;7:e50390.CrossRefPubMedPubMedCentralGoogle Scholar