Fig.4

The cGAS–STING pathway is associated with diabetes through DsbA-L. A Adiponectin promotes the expression of PPAR-regulated genes and improves insulin sensitivity in diabetic mice [140, 142]. Adiponectin activated the AMPK pathway increases fat oxidation and glucose transporter localization to the membrane [144, 145]. AMPK activation inhibits PPAR expression and TNF-α and IL-6 emission in adipose tissue [146]. In addition to directly promoting adiponectin multimerization, DsbA-L also facilitates energy homeostasis in mice, promoting energy expenditure and reducing obesity, and this regulation is independent of adiponectin. B Emerging evidence indicates that DsbA-L directly participates in the maintenance of normal mitochondrial homeostasis and inhibits the cGAS–STING pathway [14]. Obesity can promote mitochondrial damage and leak mtDNA by inhibiting DsbA-L. The leaked mtDNA, in turn, activates the cGAS–STING pathway, which in turn causes IR and metabolic syndrome. Conversely, increased DsbA-L inhibits mtDNA leakage, which in turn inhibits the cGAS–STING pathway. In the same metabolic syndrome as diabetes, we believe that this is likely to be the case as well, but experiments are still needed to confirm this. In addition, whether DsbA-L inhibits the cGAS–STING pathway exclusively by suppressing mtDNA leakage still needs to be further explored. DsbA-L disulfide bond A oxidoreductase-like protein, IR insulin resistance, MetS metabolic syndrome, mtDNA mitochondrial DNA, PPARs peroxisome proliferator-activated receptors. The solid lines and dash lines indicate the direct and indirect action, respectively