Stimulator of interferon genes: A potential target for treating type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) has emerged as a major global public health challenge. Its core pathological features, including insulin resistance and disorders of glucose and lipid metabolism, can induce multi-organ damage and substantiall reduce the quality of life of patients. The stimulator of interferon genes (STING), which is a critical signaling hub of innate immunity, plays a crucial role in the pathogenesis of T2DM. The structure and function of STING, its signal transduction, and the research progress in T2DM are summarized in this review. The findings indicate that STING is highly expressed in patients with T2DM. The activation of STING promotes the progression of T2DM by inducing mitochondrial damage, oxidative stress, autophagy disorders, inflammatory responses, macrophage polarization, imbalance of synaptic plasticity, apoptosis, and pyroptosis. A variety of inhibitors, including small-molecule compounds (fenofibrate and nicotinamide riboside), proteins (proprotein convertase subtilisin/kexin type 9 monoclonal antibody, Metrnl, Brahma-related gene 1, and irsin, interferon-stimulated gene 15), natural products (rosavin and spermidine), probiotics (ZBiotics and garlic-derived exosomes-like nanoparticles), compound drugs (sacubitril/valsartan), and nanoparticles (Mito-G and Jumonji domain-containing protein 3 inhibitory nanoparticles), can inhibit STING signal transduction, alleviate glucose dysregulation, improve lipid metabolism in T2DM, and reduce organ damage. This review provides a theoretical foundation for the development of targeted drugs, clarifies the molecular basis of STING as a novel therapeutic target for T2DM, and has important translational value for the prevention and treatment of diabetes and its complications.