Abstract
Type 1 diabetes mellitus (T1DM), or insulin dependent DM, is accompanied by decreased muscle
mass. The growth factor myostatin (MSTN) is a negative regulator of muscle growth, and a loss of
MSTN signaling has been shown to increase muscle mass and prevent the development of obesity,
insulin resistance and lipodystrophic diabetes in mice. The effects of MSTN inhibition in a T1DM
model on muscle mass and blood glucose are unknown. We asked whether MSTN inhibition
would increase muscle mass and decrease hyperglycemia in mice treated with streptozotocin
(STZ) to destroy pancreatic beta cells. After diabetes developed, mice were treated with a soluble
MSTN/activin receptor fused to Fc (ACVR2B:Fc). ACVR2B:Fc increased body weight and muscle
mass compared to vehicle treated mice. Unexpectedly, ACVR2B:Fc reproducibly exacerbated
hyperglycemia within approximately one week of administration. ACVR2B:Fc treatment also el-
evated serum levels of the glucocorticoid corticosterone. These results suggest that although
MSTN/activin inhibitors increased muscle mass, they may be counterproductive in improving
health in patients with T1DM.
Abstract
Type 1 diabetes mellitus (T1DM), or insulin dependent DM, is accompanied by decreased muscle
mass. The growth factor myostatin (MSTN) is a negative regulator of muscle growth, and a loss of
MSTN signaling has been shown to increase muscle mass and prevent the development of obesity,
insulin resistance and lipodystrophic diabetes in mice. The effects of MSTN inhibition in a T1DM
model on muscle mass and blood glucose are unknown. We asked whether MSTN inhibition
would increase muscle mass and decrease hyperglycemia in mice treated with streptozotocin
(STZ) to destroy pancreatic beta cells. After diabetes developed, mice were treated with a soluble
MSTN/activin receptor fused to Fc (ACVR2B:Fc). ACVR2B:Fc increased body weight and muscle
mass compared to vehicle treated mice. Unexpectedly, ACVR2B:Fc reproducibly exacerbated
hyperglycemia within approximately one week of administration. ACVR2B:Fc treatment also el-
evated serum levels of the glucocorticoid corticosterone. These results suggest that although
MSTN/activin inhibitors increased muscle mass, they may be counterproductive in improving
health in patients with T1DM.
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