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Muscle Growth and Function in Mouse Models of Type 2 Diabetes Mellitus

Ostler, Joseph Eldon
http://rave.ohiolink.edu/etdc/view?acc_num=osu1386022853

Abstract Details

2013, Doctor of Philosophy, Ohio State University, Integrated Biomedical Science Graduate Program.
Type 2 diabetes mellitus is associated with an accelerated muscle loss during aging, decreased muscle function, and increased disability. To better define the mechanisms causing this muscle deterioration in Type 2 diabetes, we assessed muscle weight, exercise capacity, and protein expression in db/db and TallyHo mice at ages in which they exhibited prediabetes and overt diabetes. Maximum running speeds and muscle weights were already reduced before signs of overt diabetes in db/db mice when compared to lean controls and more severely reduced in the overtly diabetic db/db mice. In contrast to db/db mice, TallyHo muscle size dramatically increased and maximum running speed was maintained during the progression from prediabetes to overt diabetes. Analysis of mechanisms that may contribute to decreased muscle weight in db/db mice demonstrated that insulin-dependent phosphorylation of enzymes that promote protein synthesis was severely blunted in db/db muscle. In addition, muscle from db/db mice with prediabetes (6 week old) and diabetes (12 week old) db/db exhibited an increase in established markers of proteasomal protein degradation: MuRF-1, Atrogin-1, and the level of polyubiquitinated proteins. Chronic treadmill training of db/db mice improved glucose tolerance, exercise capacity, and reduced markers of protein degradation, but only mildly increased muscle weight. The differences in muscle phenotype between these models of type 2 diabetes suggest that insulin resistance and chronic hyperglycemia alone are insufficient to rapidly decrease muscle size and function and that the effects of diabetes on muscle growth and function are model-dependent.
Muthu Periasamy, PhD (Advisor)
150 p.
Biology; Medicine; Physiology
muscle, diabetes, exercise, protein degradation, ubiquitin

Recommended Citations

Citations

  • Ostler, J. E. (2013). Muscle Growth and Function in Mouse Models of Type 2 Diabetes Mellitus [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1386022853

    APA Style (7th edition)

  • Ostler, Joseph. Muscle Growth and Function in Mouse Models of Type 2 Diabetes Mellitus. 2013. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1386022853.

    MLA Style (8th edition)

  • Ostler, Joseph. "Muscle Growth and Function in Mouse Models of Type 2 Diabetes Mellitus." Doctoral dissertation, Ohio State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=osu1386022853

    Chicago Manual of Style (17th edition)

osu1386022853
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© 2013, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.