PM_2.5 aggravates diabetes via the systemically activated IL-6-mediated STAT3/SOCS3 pathway in rats' liver

PM_2.5 exposure aggravates type 2 diabetes, in which inflammatory factors play an important role. In this study, we aimed to explore the mechanisms responsible for aggravating diabetes after PM_2.5 exposure, and study the roles of inflammatory factors in insulin-resistant type 2 diabetes. Our study indicated that short-time PM_2.5 exposure enhances insulin resistance in type 2 diabetic rats and significantly raises inflammatory factors, including IL-6, TNF-α, and MCP-1, in lungs. However, we found that of these inflammatory factors only IL-6 levels are elevated in blood, liver, adipose tissue, and macrophages, but not in skeletal muscle. IL-6 induced activation of the STAT3/SOCS3 pathway in liver, but not other downstream pathways including STAT1, ERK1/2, and PI3K. Both STAT3 inhibition and IL-6 neutralization effectively alleviated the disorders of glucose metabolism after PM_2.5 exposure. Taken together, this suggests that the systemic increase in IL-6 may play an important role in the deterioration of the type 2 diabetes via IL-6/STAT3/SOCS3 pathway in liver after short-time exposure to PM_2.5. Besides, we unexpectedly found a stronger resistance to the PM_2.5 exposure-induced increase in IL-6 in skeleton muscle than those of many other tissues.