Zinc and diabetes-related sarcopenia: molecular insights into muscle atrophy in diabetes

Previous reviews have discussed the pathophysiology of diabetic sarcopenia, but none have made any mention of the role of zinc (Zn). This review highlights the emerging role of Zn and Zn-related proteins as potentially important regulators of skeletal muscle mass and function, addressing their potential contributions to the pathogenesis of diabetes-related sarcopenia. Experimental models of Zn deficiency, hyperglycemia, and genetically modified Zn-associated proteins, including Zn transporters (ZnTs) and Zrt, Irt-like Proteins (ZIPs), zinc-α2-glycoprotein (ZAG), metallothioneins (MTs), and zinc finger proteins (ZFPs), suggest that Zn may contribute to the maintenance of myogenesis, protein synthesis, insulin signaling, and mitochondrial function in muscle cells. Loss or dysregulation of these proteins impairs myoblast proliferation and differentiation, increases intramuscular lipid accumulation, exacerbates oxidative stress and inflammation, and activates ubiquitin-proteasome-mediated protein degradation, thereby accelerating diabetic muscle atrophy. Zn and its related proteins may contribute to preserving skeletal muscle integrity and metabolic homeostasis under diabetic conditions. Future research should clarify the intracellular coordination of Zn flux, fiber-specific effects of Zn-handling proteins, and translational relevance to human sarcopenia, which may inform targeted nutritional and therapeutic interventions for diabetes-associated muscle loss.