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Diabetic sarcopenia: metabolic and molecular appraisal

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Abstract

Myopathy is the missing slot from the routine clinical checkup for diabetic complications. Similarly, its pathophysiological, metabolic, and molecular bases are insufficiently explored. In this review, the above issues are highlighted with a focus on skeletal muscle atrophy (also described as diabetic sarcopenia), in contrast to the normal histological, physiological, and molecular features of the muscles. Literature search using published data from different online resources was used. Several diabetic myopathy etiological factors are discussed explicitly including; inflammation and immunological responses, with emphasis on TNFα and IL-6 overproduction, oxidative stress, neuropathy and vasculopathy, aging sarcopenia, antidiabetic drugs, and insulin resistance as a denominator. The pathophysiological hallmark of diabetic muscle atrophy is the decreased muscle proteins synthesis and increased degradation. The muscle protein degradation is conveyed by 4 systems; ubiquitin-proteasome, lysosomal autophagy, caspase-3, and calpain systems, and is mostly mediated via the IL6/STAT, TNF&IL6/NFκB, myostatin/Smad2/3, and FOXO1/3 signaling pathways, while the protein synthesis inhibition is mediated via suppression of the IGF1-PI3K-Akt-mTOR, and SC-Gαi2-pathways. Moreover, the satellite cells and multilineage muscle mesenchymal progenitor cells differentiation plays a major role on the fate of the affected muscle cells by taking an adipogenic, fibrogenic, or connective tissue lineage. As a conclusion, in this article, the pathological features of diabetic sarcopenia are reviewed at gross level, while at a molecular level the normal protein turnover, signal transduction, and pathways involved in muscle atrophy are described. Finally, an integrated network describing the molecular partakers in diabetic sarcopenia is presented.

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Authors and Affiliations

  1. Medical Biochemistry and Molecular Biology, Khartoum, Sudan

    Hayder A. Giha

  2. Department of Internal Medicine, Faculty of Medicine and Health Sciences, Alneelain University, Khartoum, Sudan

    Osman A. O. Alamin

  3. Interventional Cardiology, Ahmad Gasim Cardiac Centre, Ahmad Gasim Hospital, Khartoum North, Sudan

    Osman A. O. Alamin

  4. Internal Medicine Council, Sudan Medical Specialization Board (S.M.S.B), Khartoum, Sudan

    Osman A. O. Alamin

  5. Department of Biochemistry, College of Medicine and Medical Sciences (CMMS), Arabian Gulf University (AGU), Manama, Kingdom of Bahrain

    Mai S. Sater

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Giha, H.A., Alamin, O.A.O. & Sater, M.S. Diabetic sarcopenia: metabolic and molecular appraisal. Acta Diabetol 59, 989–1000 (2022). https://doi.org/10.1007/s00592-022-01883-2

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