title: A soluble activin receptor type IIB does not improve blood glucose in streptozotocin-treated mice.
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 elevated 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.
authors.affiliation: 1. Current Addresses: Pathology Department, Stony Brook University Medical Center, Stony Brook, New York, USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: 2. Novo Nordisk Research Centre China, Changping District, Beijing, China.
authors.forename: Tingqing
authors.initials: T
authors.lastname: Guo
authors.affiliation: Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Portas
authors.affiliation: 3. Myotherapeutics, Silver Spring, Maryland, USA.
authors.forename: Alexandra C
authors.initials: AC
authors.lastname: McPherron
mesh_terms: D030301:Activin Receptors, Type II / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009135:Muscular Diseases; D055435:Myostatin / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D013311:Streptozocin / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; C525912:Mstn protein, mouse; D055435:Myostatin; D011994:Recombinant Proteins; D013311:Streptozocin; D030301:Activin Receptors, Type II; C425584:activin receptor type II-B
keywords: activin receptor; glucocorticoid; muscle hypertrophy; myostatin; type 1 diabetes