TY - JOUR
T1 - Targeting SGK1 in diabetes
AU - Lang, Florian
AU - Görlach, Agnes
AU - Vallon, Volker
N1 - Funding Information:
Studies in the authors laboratory are funded by the Deutsche Forschungsgemeinschaft (GRK 1302, to F Lang, GO709/4-4 to A Görlach) and the National Institutes of Health (NIH “DK56248 & DK28602” to V Vallon).
PY - 2009/11
Y1 - 2009/11
N2 - Compelling evidence is accumulating indicating a pathophysiological role of the serum-and-glucocorticoid-inducible-kinase-1 (SGK1) in the development and complications of diabetes. SGK1 is ubiquitously expressed with exquisitely high transcriptional volatility. Stimulators of SGK1 expression include hyperglycemia, cell shrinkage, ischemia, glucocorticoids and mineralocorticoids. SGK1 is activated by insulin and growth factors via PI3K, 3-phosphoinositide dependent kinase PDK1 and mTOR. SGK1 activates ion channels (including ENaC, TRPV5, ROMK, KCNE1/KCNQ1 and CLCKa/Barttin), carriers (including NCC, NKCC, NHE3, SGLT1 and EAAT3), and the Na+/K+-ATPase. It regulates the activity of several enzymes (e.g., glycogen-synthase-kinase-3, ubiquitin-ligase Nedd4-2, phosphomannose-mutase-2), and transcription factors (e.g., forkhead-transcription-factor FOXO3a, β-catenin and NF-κB). A common SGK1 gene variant (∼ 3 - 5% prevalence in Caucasians, ∼ 10% in Africans) is associated with increased blood pressure, obesity and type 2 diabetes. In patients suffering from type 2 diabetes, SGK1 presumably contributes to fluid retention and hypertension, enhanced coagulation and increased deposition of matrix proteins leading to tissue fibrosis such as diabetic nephropathy. Accordingly, targeting SGK1 may favourably influence occurrence and course of type 2 diabetes.
AB - Compelling evidence is accumulating indicating a pathophysiological role of the serum-and-glucocorticoid-inducible-kinase-1 (SGK1) in the development and complications of diabetes. SGK1 is ubiquitously expressed with exquisitely high transcriptional volatility. Stimulators of SGK1 expression include hyperglycemia, cell shrinkage, ischemia, glucocorticoids and mineralocorticoids. SGK1 is activated by insulin and growth factors via PI3K, 3-phosphoinositide dependent kinase PDK1 and mTOR. SGK1 activates ion channels (including ENaC, TRPV5, ROMK, KCNE1/KCNQ1 and CLCKa/Barttin), carriers (including NCC, NKCC, NHE3, SGLT1 and EAAT3), and the Na+/K+-ATPase. It regulates the activity of several enzymes (e.g., glycogen-synthase-kinase-3, ubiquitin-ligase Nedd4-2, phosphomannose-mutase-2), and transcription factors (e.g., forkhead-transcription-factor FOXO3a, β-catenin and NF-κB). A common SGK1 gene variant (∼ 3 - 5% prevalence in Caucasians, ∼ 10% in Africans) is associated with increased blood pressure, obesity and type 2 diabetes. In patients suffering from type 2 diabetes, SGK1 presumably contributes to fluid retention and hypertension, enhanced coagulation and increased deposition of matrix proteins leading to tissue fibrosis such as diabetic nephropathy. Accordingly, targeting SGK1 may favourably influence occurrence and course of type 2 diabetes.
KW - coagulation
KW - fibrosis
KW - hypertension
KW - inflammation
KW - metabolic syndrome
UR - http://www.scopus.com/inward/record.url?scp=73449101166&partnerID=8YFLogxK
U2 - 10.1517/14728220903260807
DO - 10.1517/14728220903260807
M3 - Review article
C2 - 19764891
AN - SCOPUS:73449101166
SN - 1472-8222
VL - 13
SP - 1303
EP - 1311
JO - Expert Opinion on Therapeutic Targets
JF - Expert Opinion on Therapeutic Targets
IS - 11
ER -
