Preventive effects of turmeric against HFD/STZ-induced type 2 diabetes in mice by activating IRS1/PI3K/Akt signaling in association with gut microbiota metabolism

This study is the first to investigate the antidiabetic effect of turmeric powder (TP) and its underlying molecular mechanism in type 2 diabetes mellitus (T2DM) mice. The T2DM mice were supplemented with or without TP (8%) for 8 weeks. The results indicated that the glucolipid metabolism disorder and insulin resistance in T2DM mice were significantly ameliorated through supplementation with TP. The consumption of TP also ameliorated the T2DM-induced gut microbiota dysbiosis, as reflected by a dramatic increase in the relative abundance of beneficial bacteria such as <i>Bacteroides</i>, <i>Rikenella</i> and <i>Allobaculum</i> at the genus level. Besides, TP significantly increased the colonic levels of short-chain fatty acids (SCFAs) and subsequently activated the IRS1/PI3K/Akt and AMPK-mediated gluconeogenesis signaling pathways to improve insulin resistance in T2DM mice. Interestingly, TP-activated IRS1/PI3K/Akt and AMPK-mediated gluconeogenesis signaling pathways were highly correlated with the reconstruction of the gut microbiome and the formation of SCFAs. Collectively, these findings, for the first time, highlight a novel antidiabetic mechanism of TP by alleviating intestinal microbiota dysbiosis and promoting SCFA production to trigger the IRS1/PI3K/Akt and AMPK-mediated gluconeogenesis signaling axis.