Interplay between sarcopenia and type 2 diabetes: mechanisms, implications, and therapeutic prospects

Figures

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  Fig. 1. Factors contributing to sarcopenia: an overview of neuromuscular impairment and age-related influences. Several diseases, such as COPD, diabetes, chronic kidney disease, and chronic liver disease, exacerbate sarcopenia. COPD chronic obstructive pulmonary disease; neuromuscular junction.

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  Fig. 2. Systems overview of metabolic, inflammatory, and nutritional factors in sarcopenia–T2D interaction. This schematic illustrates the bidirectional relationship between sarcopenia and T2D, highlighting key contributing factors including insulin resistance, chronic inflammation, oxidative stress, and nutritional imbalance. Impaired insulin signaling and reduced GLUT4 translocation lead to decreased glucose uptake and enhanced muscle protein degradation, while proinflammatory cytokines (e.g., IL-6, TNF-α) further accelerate muscle catabolism via NF-κB and STAT3 pathways. Hyperglycemia-induced oxidative stress and advanced glycation end products exacerbate mitochondrial dysfunction and structural muscle damage. In parallel, malnutrition, reduced protein intake, and vitamin D deficiency contribute to muscle loss and metabolic dysregulation. T2D type 2 diabetes.

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  Fig. 3. Metabolic and pathophysiological perspectives in the relationship between sarcopenia and T2D. This figure illustrates the metabolic and pathophysiological mechanisms underlying the intricate relationship between sarcopenia and T2D. It highlights multifaceted interactions between insulin resistance, inflammation, oxidative stress, advanced glycation end products (AGEs), and nutritional factors in the development and progression of sarcopenia in individuals with T2D. It also depicts the cellular and molecular pathways implicated in sarcopenia–T2D comorbidity, including dysregulation of the GLUT4 pathway, altered myostatin regulation, and enhanced activity of the ubiquitin-proteasome pathway. T2D type 2 diabetes.

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  Fig. 4. Molecular mechanisms underlying sarcopenia and T2D. The overall schematic presentation illustrates the molecular mechanisms proposed to contribute to the association between sarcopenia and T2D. The central pathways involved include glucose metabolism and insulin resistance, which play critical roles in regulating protein synthesis and degradation in muscle tissues. The various signaling cascades are depicted, highlighting their regulatory effects on the intricate balance between the synthesis and degradation of muscle protein. T2D type 2 diabetes.

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  Fig. 5. Depiction of molecular interplay between impaired insulin signaling and WWP1-mediated ubiquitination in skeletal muscle. The disruption of the IRS-1/PI3K/Akt pathway limits GLUT4 translocation, while hyperglycemia-driven activation of WWP1 exacerbates insulin resistance and protein degradation, collectively contributing to muscle wasting in sarcopenia and T2D. T2D type 2 diabetes, WWP1 WW domain-containing protein 1.