{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T00:40:54Z","timestamp":1784335254157,"version":"3.55.0"},"reference-count":59,"publisher":"Oxford University Press (OUP)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The epithelial Na+ channel (ENaC) is decisive for sodium reabsorption by the aldosterone-sensitive distal nephron (ASDN) of the kidney. ENaC is regulated by the serum- and glucocorticoid-inducible kinase 1 (SGK1), a kinase genomically upregulated by several hormones including glucocorticoids and mineralocorticoids. SGK1 is activated by the serine\/threonine kinase mammalian target of rapamycin (mTOR) isoform mTORC2. SGK1 knockout (sgk1\u2212\/\u2212 mice) impairs renal Na+ retention during salt depletion. The mTOR catalytic site inhibitor, PP242, but not mTORC1 inhibitor rapamycin, inhibits ENaC, decreases Na+ flux in isolated perfused tubules and induces natriuresis in wild-type mice. PP242 does not lead to further impairment of Na+ reabsorption in sgk1\u2212\/\u2212 mice. The mTORC2\/SGK1 sensitive renal Na+ retention leads to extracellular volume expansion with increase of blood pressure. A SGK1 gene variant (prevalence \u223c3\u20135% in Caucasians, \u223c10% in Africans) predisposes to hypertension, stroke, obesity and type 2 diabetes. Future studies will be required to define the role of mTORC2 in the regulation of further SGK1 sensitive transport proteins, such as further ion channels, carriers and the Na+\/K+-ATPase. Moreover, studies are required disclosing the impact of mTORC2 on SGK1 sensitive disorders, such as hypertension, obesity, diabetes, thrombosis, stroke, inflammation, autoimmune disease, fibrosis and tumour growth.<\/jats:p>","DOI":"10.1093\/ndt\/gfv270","type":"journal-article","created":{"date-parts":[[2015,7,10]],"date-time":"2015-07-10T21:04:29Z","timestamp":1436562269000},"page":"200-205","source":"Crossref","is-referenced-by-count":30,"title":["Regulation of the epithelial Na+ channel by the mTORC2\/SGK1 pathway"],"prefix":"10.1093","volume":"31","author":[{"given":"Florian","family":"Lang","sequence":"first","affiliation":[{"name":"University of T\u00fcbingen 1 Department of Physiology , , T\u00fcbingen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Pearce","sequence":"additional","affiliation":[{"name":"University of California at San Francisco 2 Division of Nephrology, Department of Medicine , , San Francisco, CA 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