FGF21 regulates the sensitivity of hepatic insulin

Type 2 diabetes is one of the typical chronic disease; insulin resistance plays an important role in the occurrence and development of diabetes. Develop high insulin sensitivity of target drugs; it is currently one of the most effective ways to improve the effectiveness of the treatment of diabetes. Studies show that, FGF21 is produced by the liver and a major hormone secreted by administering FGF21 treatment or overexpression of FGF21 in vivo, can be reduced in obese rodents, monkeys and humans suffering from hyperinsulinemia, insulin resistance, and the risk of hyperglycemia and other diseases. Current research on FGF21 increasing year by year, but about FGF21 in vivo molecular mechanism of action is still not clear.

A recent study by the depth of in vitro and in vivo experiments in mice found that when the liver-specific knockdown of FGF21 receptor βKlotho, insulin sensitivity and blood glucose lowering effect of FGF21 will be reduced; in the mouse liver, primary hepatocytes and human liver cell lines, FGF21 can suppress an increase in mTORC1 activity by insulin resistance caused prove FGF21 is a mTORC1 negative regulatory factor; experiments also found that when over-upon expression mTORC1 downstream key molecule S6K1, FGF21 small insulin sensitizing effect of rat liver and primary liver cells disappear, further studies have shown that, FGF21 is by activating the liver and primary hepatocytes insulin signaling pathway, thereby promoting glycogen synthesis, gene knockout TSC1 activates mTORC1, thereby inhibiting FGF21 the primary role in promoting liver glycogen synthesis right, inferred, FGF21 may be to promote glycogen synthesis by inhibiting mTORC1.

The study reveals the FGF21 in improved hepatic insulin sensitivity and glucose metabolism in balance, the direct effect on the liver, FGF21 may be as complex mTORC1 inhibitor, by inhibiting the activity of mTORC1 complex, increased hepatic insulin sensitivity, promote liver glycogen storage to increase the utilization of glucose, which regulate the body's metabolism of glucose homeostasis.

The study uncovers the role of FGF21 in the liver and liver cells in the molecular mechanism, providing a new theoretical foundation. It also shows that deep discussion on FGF21-mTORC1 signaling pathway will develop new research ideas for exploring new drug targets of treatment for insulin resistance and type 2 diabetes and other metabolic diseases.

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