The serum- and glucocorticoid-induced kinase (SGK1) is a serine/threonine kinase structurally related to the family of AGC kinases. SGK1 participates in many cellular processes, including the regulation of epithelial sodium channel (ENaC) activity, which constitutes the rate-limiting step in transtepithelial sodium transport in the distal nephron. In addition to its physiological functions, it has been proposed that an excess of SGK1 activity could be a contributing factor to a number of pathological conditions, including hypertension and diabetic nephropathy. We are using mouse models to explore the role of this kinase as a determinant of hypertension and renal damage progression. Specifically, we have developed a SGK1 transgenic mouse and we are currently studying the effects of the transgene in renal sodium reabsorption under conditions of normal or high-salt diets. We are also using a mouse model of type 2 diabetes (db/db mice) to explore the role of SGK1 in the development of diabetic nephropathy. Our data show that SGK1 is overexpressed in the kidneys of db/db animals. Overexpression starts with the development of hyperglycemia, consistent with a possible role in the progression of renal damage. We are currently producing compound mutant mice with SGK1 overexpression in db/db background. This model will allow us to determine whether SGK1 accelerates the progression of diabetic nephropathy.

This work has been funded by grants from Gobierno de Canarias (2004/081) and Fundación Canaria de Investigación y Salud (FUNCIS, PI 88/04), Spain, to D.A.R.