A Disruptor of Insulin Signaling

Science's STKE  10 Jun 2003:
Vol. 2003, Issue 186, pp. tw223-TW223
DOI: 10.1126/stke.2003.186.tw223

The protein kinase Akt is a key component in insulin signaling. Du et al. searched for proteins that directly interacted with Akt and found a protein they call TRB3, a mammalian homolog of the Drosophila tribbles protein, that functions as an inhibitor of the kinase. The amount of TRB3 RNA in livers from diabetic mice was increased compared with that in the wild type. Infection of mice or of rat FAO hepatoma cells with adenovirus expressing TRB3 caused hyperglycemia and reduced responses to insulin, respectively. The results establish TRB3 as component in metabolic control by insulin and as a potential therapeutic target for treatment of type II diabetes.

K. Du, S. Herzig, R. N. Kulkarni, M. Montminy, TRB3: A tribbles homolog that inhibits Akt/PKB activation by insulin in liver. Science 300, 1574-1577 (2003). [Abstract] [Full Text]