A myostatin inhibitory antibody combined with insulin, partially rescues the musculoskeletal phenotype of female insulin-deficient diabetic mice.

Introduction: Type 1 diabetes is associated with deficits in both skeletal muscle and bone. Inhibition of myostatin, a negative regulator of muscle mass, was explored as a druggable target to improve the musculoskeletal phenotype associated with insulin-deficient diabetes in female mice. Methods: We investigated whether administration of an inhibitory myostatin antibody (MyoAb) in streptozotocin-induced diabetes in female mice is protective for skeletal muscle and bone. DBA/2J female mice were injected with low-dose streptozotocin or with citrate buffer (vehicle). Subsequently, mice were implanted with insulin-containing or vehicle pellets, with groups being randomized to myostatin or control antibody for 8 weeks. At study end, body composition and Results: Glycated hemoglobin was significantly higher in diabetic mice compared to non-diabetic mice and diabetic mice treated with insulin. In diabetic mice, the combination of insulin and MyoAb resulted in higher lean mass, higher average gastrocnemius weight and larger muscle fiber size (Type IIB, IIX and hybrid fibers) compared to no treatment. Conclusions: Myostatin inhibition when used in conjunction with insulin treatment improves muscle mass and trabecular bone properties in a mouse model of insulin-deficient diabetes in female mice.