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© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Type 1 Diabetes Mellitus (T1D) is a disease characterized by the destruction of pancreatic beta cells. The subsequent loss of insulin production results in hyperglycemia, muscle wasting, and vascular dysfunction. Due to an inability to appropriately maintain glucose homeostasis, patients afflicted with T1D suffer from increased morbidity and early mortality. Skeletal muscle is the body’s largest metabolic reservoir, absorbing significant amounts of glucose from the bloodstream and physical exercise is known to improve and prevent the progression of pathological outcomes, but many T1D patients are unable to exercise at a level that conveys benefit. Thus, directly targeting muscle mass and function may prove beneficial for improving T1D patient outcomes, independent of exercise. A potent negative regulator of skeletal muscle has been identified as being upregulated in T1D patients, namely the myokine myostatin. Our hypothesis is that targeting myostatin (via genetic deletion) will prevent glucose dysfunction in a T1D model, preserve skeletal muscle function, and protect against vascular and renal dysfunction. Our methods utilized adult male mice with (WT) and without myostatin (Myo KO), in combination with the chemical induction of T1D (streptozotocin). Experimental outcomes included the assessment of glucose homeostasis (plasma glucose, HbA1c, IGTT), metabolism, muscle function (in vivo plantarflexion), and skeletal muscle vascular function (ex vivo pressure myography). Our results described systemic benefits from myostatin deletion in the T1D model, independent of insulin, including the following: inhibition of T1D-induced increases in plasma glucose, prevention of functional deficits in muscle performance, and preservation of fluid dynamics. Further, endothelial function was preserved with myostatin deletion. Taken together, these data inform upon the use of myostatin inhibition as a therapeutic target for effective treatment and management of the cardiometabolic and skeletal muscle dysfunction that occurs with T1D.

Details

Title
Targeting Myostatin as an Adjunct Treatment for the Preservation of Cardiometabolic and Skeletal Muscle Function in Type 1 Diabetes
Author
Nunan, Emily 1 ; Huff, Denton R 1 ; Gore, Jillian L 1 ; Wright, Carson L 1   VIAFID ORCID Logo  ; Harris, Tag 1   VIAFID ORCID Logo  ; Butler, Landon 1 ; Padgett, Caleb A 2   VIAFID ORCID Logo  ; Rochowski, Matthew T 1 ; Lovern, Pamela C 1 ; Boolani Ali 3   VIAFID ORCID Logo  ; Valdez Cammi 4   VIAFID ORCID Logo  ; Butcher, Joshua T 1   VIAFID ORCID Logo 

 Department of Physiological Sciences, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078, USA 
 Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA 
 Human Performance and Nutrition Research Institute, Oklahoma State University, Stillwater, OK 74078, USA; [email protected] 
 Department of Physical Sciences, Northeastern State University, Tahlequah, OK 74464, USA; [email protected] 
First page
4830
Publication year
2025
Publication date
2025
Publisher
MDPI AG
ISSN
16616596
e-ISSN
14220067
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3212116383
Copyright
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.