Editors' ChoiceMEDICINE

Human Insulin Signaling

Science's STKE  01 Jun 2004:
Vol. 2004, Issue 235, pp. tw200-TW200
DOI: 10.1126/stke.2352004TW200

The most common forms of type 2 diabetes are thought to arise from the interaction of many different genes and life-style factors. As is true for other complex diseases, the genetic factors contributing to the pathogenesis of diabetes are more readily identified by studying rare, monogenic forms of the disease. George et al. find that a family showing autosomal-dominant inheritance of severe insulin resistance and diabetes carries a mutation in the serine-threonine kinase AKT2, which inactivates its function. Earlier studies of mice had identified AKT2 as a key player in the insulin signaling pathway, and the new genetic data underscore the protein's important role in human diabetes.

S. George, J. J. Rochford, C. Wolfrum, S. L. Gray, S. Schinner, J. C. Wilson, M. A. Soos, P. R. Murgatroyd, R. M. Williams, C. L. Acerini, D. B. Dunger, D. Barford, A. M. Umpleby, N. J. Wareham, H. Alban Davies, A. J. Schafer, M. Stoffel, S. O'Rahilly, I. Barroso, A family with severe insulin resistance and diabetes mellitus due to a missense mutation in AKT2. Science 304, 1325-1328 (2004). [Abstract] [Full Text]