Molecular Medicine (Jun 2024)

The analysis of the skeletal muscle metabolism is crucial for designing optimal exercise paradigms in type 2 diabetes mellitus

  • Elias Abi Akar,
  • Laure Weill,
  • Mirella El Khoury,
  • Cédric Caradeuc,
  • Gildas Bertho,
  • Suzan Boutary,
  • Cynthia Bezier,
  • Zoé Clerc,
  • Delphine Sapaly,
  • Sabrina Bendris,
  • Flore Cheguillaume,
  • Nicolas Giraud,
  • Assaad A. Eid,
  • Frédéric Charbonnier,
  • Olivier Biondi

DOI
https://doi.org/10.1186/s10020-024-00850-7
Journal volume & issue
Vol. 30, no. 1
pp. 1 – 16

Abstract

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Abstract Background Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease that commonly results from a high-calorie diet and sedentary lifestyle, leading to insulin resistance and glucose homeostasis perturbation. Physical activity is recommended as one first-line treatment in T2DM, but it leads to contrasted results. We hypothesized that, instead of applying standard exercise protocols, the prescription of personalized exercise programs specifically designed to reverse the potential metabolic alterations in skeletal muscle could result in better results. Methods To test this hypothesis, we drew the metabolic signature of the fast-twitch quadriceps muscle, based on a combined unbiased NMR spectroscopy and RT-qPCR study, in several T2DM mouse models of different genetic background (129S1/SvImJ, C57Bl/6J), sex and aetiology (high-fat diet (HFD) or HFD/Streptozotocin (STZ) induction or transgenic MKR (FVB-Tg Ckm-IGF1R*K1003R)1Dlr/J) mice. Three selected mouse models with unique muscular metabolic signatures were submitted to three different swimming-based programs, designed to address each metabolic specificity. Results We found that depending on the genetic background, the sex, and the mode of T2DM induction, specific muscular adaptations occurred, including depressed glycolysis associated with elevated PDK4 expression, shift to β-oxidation, or deregulation of amino-acid homeostasis. Interestingly, dedicated swimming-based exercises designed to restore specific metabolic alterations in muscle were found optimal in improving systemic T2DM hallmarks, including a significant reduction in insulin resistance, the improvement of glucose homeostasis, and a delay in sensorimotor function alterations. Conclusion The muscle metabolism constitutes an important clue for the design of precision exercises with potential clinical implications for T2DM patients.

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