PM2.5 aggravates diabetes via the systemically activated IL-6-mediated STAT3/SOCS3 pathway in rats' liver.

ABSTRACT

PM2.5 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 PM2.5 exposure, and study the roles of inflammatory factors in insulin-resistant type 2 diabetes. Our study indicated that short-time PM2.5 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 PM2.5 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 PM2.5. Besides, we unexpectedly found a stronger resistance to the PM2.5 exposure-induced increase in IL-6 in skeleton muscle than those of many other tissues.