title: SGK, renal function and hypertension.
abstract: Serum- and glucocorticoid-inducible kinase 1 (SGK1) is expressed following cell stress and exposure to a variety of hormones including glucocorticoids and mineralocorticoids. It is activated by insulin and growth factors via phosphatidylinositol-3-kinase and the 3-phosphoinositide-dependent kinase PDK1. SGK1 enhances the activity of a variety of ion channels such as ENaC, TRPV5, ROMK, KCNE1/KCNQ1 and ClCKb; carriers such as NHE3, NKCC2, NCC and SGLT1; as well as the Na+/K+-ATPase. SGK1 contributes to Na+ retention and K+ elimination of the kidney as well as mineralocorticoid stimulation of salt appetite. A certain SGK1 gene variant (combined polymorphisms in intron 6 [I6CC] and in exon 8 [E8CC/CT]) is associated with moderately enhanced blood pressure. The SGK1 gene variant has been shown to affect 3%-5% of whites and some 10% of Africans. The gene variant sensitizes the carriers to the hypertensive effects of hyperinsulinemia. Moreover, the SGK1 gene variant is associated with increased body mass index, presumably a result of enhanced SGLT1 activity with accelerated intestinal glucose absorption. Obesity predisposes the carriers of the gene variant to development of type 2 diabetes. Moreover, SGK1 stimulates coagulation. Thus, SGK1 may participate in the pathogenesis of metabolic syndrome or syndrome X, a condition characterized by the coincidence of essential hypertension, procoagulant state, obesity, insulin resistance and hyperinsulinemia.
authors.affiliation: Department of Physiology, University of Tuebingen, Tuebingen, Germany. florian.lang@uni-tuebingen.de
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
authors.forename: Dan Yang
authors.initials: DY
authors.lastname: Huang
authors.forename: Volker
authors.initials: V
authors.lastname: Vallon
mesh_terms: D000818:Animals; D053503:Epithelial Sodium Channels / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000209:etiology*; D017874:Immediate-Early Proteins / Q000502:physiology*; D007668:Kidney / Q000502:physiology*; D024821:Metabolic Syndrome / Q000209:etiology; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D012964:Sodium / Q000378:metabolism; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D053503:Epithelial Sodium Channels; D017874:Immediate-Early Proteins; D017346:Protein Serine-Threonine Kinases; D012964:Sodium; D000099184:Serum-Glucocorticoid Regulated Kinases