{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T18:59:59Z","timestamp":1782327599933,"version":"3.54.5"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2023,10,26]],"date-time":"2023-10-26T00:00:00Z","timestamp":1698278400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017618","name":"Division of Diabetes, Endocrinology, and Metabolic Diseases","doi-asserted-by":"publisher","award":["K08DK124566"],"award-info":[{"award-number":["K08DK124566"]}],"id":[{"id":"10.13039\/100017618","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P30 GM127211"],"award-info":[{"award-number":["P30 GM127211"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007472","name":"University of Kentucky","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007472","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007472","name":"University of Kentucky","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007472","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["asbmr.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JBMR Plus"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Type 1 diabetes (T1D) is associated with low bone and muscle mass, increased fracture risk, and impaired skeletal muscle function. Myostatin, a myokine that is systemically elevated in humans with T1D, negatively regulates muscle mass and bone formation. We investigated whether pharmacologic myostatin inhibition in a mouse model of insulin\u2010deficient, streptozotocin (STZ)\u2010induced diabetes is protective for bone and skeletal muscle. DBA\/2J male mice were injected with low\u2010dose STZ (diabetic) or vehicle (non\u2010diabetic). Subsequently, insulin or palmitate Linbits were implanted and myostatin (REGN647\u2010MyoAb) or control (REGN1945\u2010ConAb) antibody was administered for 8\u2009weeks. Body composition and contractile muscle function were assessed in vivo. Systemic myostatin, P1NP, CTX\u2010I, and glycated hemoglobin (HbA1c) were quantified, and gastrocnemii were weighed and analyzed for muscle fiber composition and gene expression of selected genes. Cortical and trabecular parameters were analyzed (micro\u2010computed tomography evaluations of femur) and cortical bone strength was assessed (three\u2010point bending test of femur diaphysis). In diabetic mice, the combination of insulin\/MyoAb treatment resulted in significantly higher lean mass and gastrocnemius weight compared with MyoAb or insulin treatment alone. Similarly, higher raw torque was observed in skeletal muscle of insulin\/MyoAb\u2010treated diabetic mice compared with MyoAb or insulin treatment. Additionally, muscle fiber cross\u2010sectional area (CSA) was lower with diabetes and the combination treatment with insulin\/MyoAb significantly improved CSA in type II fibers. Insulin, MyoAb, or insulin\/MyoAb treatment improved several parameters of trabecular architecture (eg, bone volume fraction [BV\/TV], trabecular connectivity density [Conn.D]) and cortical structure (eg, cortical bone area [Ct. Ar.], minimum moment of inertia [Imin]) in diabetic mice. Lastly, cortical bone biomechanical properties (stiffness and yield force) were also improved with insulin or MyoAb treatment. In conclusion, pharmacologic myostatin inhibition is beneficial for muscle mass, muscle function, and bone properties in this mouse model of T1D and its effects are both independent and additive to the positive effects of insulin. \u00a9 2023 The Authors.\n                    <jats:italic>JBMR Plus<\/jats:italic>\n                    published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.\n                  <\/jats:p>","DOI":"10.1002\/jbm4.10833","type":"journal-article","created":{"date-parts":[[2023,10,27]],"date-time":"2023-10-27T00:10:02Z","timestamp":1698365402000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Pharmacologic Inhibition of Myostatin With a Myostatin Antibody Improves the Skeletal Muscle and Bone Phenotype of Male Insulin\u2010Deficient Diabetic Mice"],"prefix":"10.1093","volume":"7","author":[{"given":"R Clay","family":"Bunn","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Barnstable Brown Diabetes Center University of Kentucky  Lexington KY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reuben","family":"Adatorwovor","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, College of Public Health University of Kentucky  Lexington KY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca R","family":"Smith","sequence":"additional","affiliation":[{"name":"Sanders\u2010Brown Center on Aging University of Kentucky  Lexington KY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip D","family":"Ray","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Kentucky  Lexington KY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E","family":"Fields","sequence":"additional","affiliation":[{"name":"College of Agriculture, Food and Environment University of Kentucky  Lexington KY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander R","family":"Keeble","sequence":"additional","affiliation":[{"name":"Center for Muscle Biology University of Kentucky  Lexington KY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher S","family":"Fry","sequence":"additional","affiliation":[{"name":"Center for Muscle Biology University of Kentucky  Lexington KY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sasidhar","family":"Uppuganti","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Vanderbilt University Medical Center  Nashville TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffry S","family":"Nyman","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Vanderbilt University Medical Center  Nashville TN USA"},{"name":"Department of Veterans Affairs Tennessee Valley Healthcare System  Nashville TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John L","family":"Fowlkes","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Barnstable Brown Diabetes Center University of Kentucky  Lexington KY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0556-3975","authenticated-orcid":false,"given":"Evangelia","family":"Kalaitzoglou","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Barnstable Brown Diabetes Center University of Kentucky  Lexington KY 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