INS and serum lipopolysaccharide activity: Metformin has evidenced that improving the expression of tight junction occludin-1 in the gut increased the abundance of beneficial bacteria, such as Lactobacillus and Akkermansia muciniphila, attenuated endotoxemia and oxidative stress, and promoted the anti-oxidative Nrf2 system, resulting in an improved glucose metabolism and insulin signaling pathway in the liver and the muscles of HFD-fed mice [47].