Cited by 102Muscle Physiology and DisordersMuscle metabolism and nutritionMetabolism, Diabetes, and Cancer

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Effects of insulin resistance on skeletal muscle growth and exercise capacity in type 2 diabetic mouse models

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Ostler, Joseph E., Maurya, Santosh K., Dials, Justin, Roof, Steve R., Devor, Steven T., Ziolo, Mark T., Periasamy, Muthu·2014·American Journal of Physiology-Endocrinology and Metabolism

DOI 10.1152/ajpendo.00277.2013PMC PMC3948983

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Abstract

Type 2 diabetes mellitus is associated with an accelerated muscle loss during aging, decreased muscle function, and increased disability. To better understand the mechanisms causing this muscle deterioration in type 2 diabetes, we assessed muscle weight, exercise capacity, and biochemistry in db/ db and TallyHo mice at prediabetic and overtly diabetic ages. Maximum running speeds and muscle weights were already reduced in prediabetic db/ db mice when compared with 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, prediabetic (6-wk-old) and diabetic (12-wk-old) db/ db muscle exhibited an increase in a marker of proteasomal protein degradation, the level of polyubiquitinated proteins. Chronic treadmill training of db/ db mice improved glucose tolerance and exercise capacity, 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 animal model-dependent.

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Authors: Ostler, J. E., Maurya, S. K., Dials, J., Roof, S. R., Devor, S. T., Ziolo, M. T., & Periasamy, M.
Affiliations: The Ohio State University (US)
Corresponding author: Periasamy, Muthu
ORCID: Maurya, Santosh K.
Roof, Steve R.
Ziolo, Mark T.
Periasamy, Muthu
Venue: American Journal of Physiology-Endocrinology and Metabolism
Publisher: American Physiological Society
Published: 2014-03-15
Volume: 306
Issue: 6
Pages: E592-E605
ISSN: 0193-1849 (ISSN-L)
1522-1555
DOI: 10.1152/ajpendo.00277.2013
PMC: PMC3948983
OpenAlex: W2047831763
Cited by: 102
References: 66
Citations by year: 2026: 5 · 2025: 12 · 2024: 10 · 2023: 8 · 2022: 12 · 2021: 12 · 2020: 8 · 2019: 8 · 2018: 9 · 2017: 6 · 2016: 4 · 2015: 5 · 2014: 3
FWCI: 2.46
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: American Diabetes Association
National Institutes of Health
National Heart, Lung, and Blood Institute (R01HL088555)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords: insulin resistance, type 2 diabetes, skeletal muscle growth, exercise capacity, db/db mice, prediabetes, muscle atrophy, protein synthesis, protein degradation, polyubiquitinated proteins, treadmill training, glucose tolerance, hyperglycemia, animal model comparison
MeSH terms: Animals, Diabetes Mellitus, Type 2, Disease Models, Animal, Hypoglycemic Agents, Insulin, Insulin Resistance, Male, Mice, Inbred C57BL, Mice, Mutant Strains, Motor Activity, Phosphorylation, Physical Endurance, Prediabetic State, Protein Processing, Post-Translational, Muscle, Skeletal, Animals, Outbred Strains, Muscle Development, Proteasome Endopeptidase Complex, Mice, Sarcopenia

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Effects of insulin resistance on skeletal muscle growth and exercise capacity in type 2 diabetic mouse models

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