Year: 2013
Type: article
Abstract: 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 iii insufficient to rapidly decrease muscle size and function and that the effects of diabetes on muscle growth and function are model-dependent.alone; multiple pathways and systems work together to achieve the desired effect.Similarly, none of what I have learned or accomplished in research or life has been possible alone.I appreciate the regular input and feedback of my research mentor, Dr.Periasamy, and his lack of fear in critiquing our own ideas and work.In addition, I am grateful for Dr. Santosh Maurya, who I was fortunate to be able to work closely with.I am grateful for his willingness to discuss ideas, troubleshoot, and perform experiments, especially in our study of proteasomal protein degradation.I was also fortunate to have a supportive environment of fellow graduate and postdoctoral students that were each kind to give their support, feedback, friendship, time for proofreading, and to share insight into experiments and life:
Author: Joseph E. Ostler
Institution: The Ohio State University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2287633054