TLR4 and Hyperglycemia: Metformin, an AMPK activator, has been found to facilitate clearance of NETs (173), decrease the production of pro-inflammatory cytokines and nuclear factors (such as NF-κB) when bound to certain Toll-like-receptors (such as TLR4) (174), and increase insulin sensitivity to reduce hyperglycemia by downregulating NF-κB and TLR4 (175).