Figure 5.

Serine phosphorylation in Dahl S rats precipitates insulin resistance. Dahl S rats are postulated in the current proposal to have increased serine phosphorylation of insulin receptor substrate-1 and/or 2 (IRS-1 and/or-2) on critical sites such as Ser 312, 616, 307, and 323. This in turn reduces their ability to bind and activate either the insulin receptor or the phosphoinositol 3-kinase, resulting in reduced insulin-stimulated glucose transport activity and other events downstream of PI3K.