title: SGK1-sensitive renal tubular glucose reabsorption in diabetes.
abstract: The hyperglycemia of diabetes mellitus increases the filtered glucose load beyond the maximal tubular transport rate and thus leads to glucosuria. Sustained hyperglycemia, however, may gradually increase the maximal renal tubular transport rate and thereby blunt the increase of urinary glucose excretion. The mechanisms accounting for the increase of renal tubular glucose transport have remained ill-defined. A candidate is the serum- and glucocorticoid-inducible kinase SGK1. The kinase has been shown to stimulate Na(+)-coupled glucose transport in vitro and mediate the stimulation of electrogenic intestinal glucose transport by glucocorticoids in vivo. SGK1 expression is confined to glomerula and distal nephron in intact kidneys but may extend to the proximal tubule in diabetic nephropathy. To explore whether SGK1 modifies glucose transport in diabetic kidneys, Akita mice (akita(+/-)), which develop spontaneous diabetes, have been crossbred with gene-targeted mice lacking SGK1 on one allele (sgk1(+/-)) to eventually generate either akita(+/-)/sgk1(-/-) or akita(+/-)/sgk1(+/+) mice. Both akita(+/-)/sgk1(-/-) and akita(+/-)/sgk1(+/+) mice developed profound hyperglycemia (>20 mM) within approximately 6 wk. Body weight and plasma glucose concentrations were not significantly different between these two genotypes. However, urinary excretion of glucose and urinary excretion of fluid, Na(+), and K(+), as well as plasma aldosterone concentrations, were significantly higher in akita(+/-)/sgk1(-/-) than in akita(+/-)/sgk1(+/+) mice. Studies in isolated perfused proximal tubules revealed that the electrogenic glucose transport was significantly lower in akita(+/-)/sgk1(-/-) than in akita(+/-)/sgk1(+/+) mice. The data provide the first evidence that SGK1 participates in the stimulation of renal tubular glucose transport in diabetic kidneys.
authors.affiliation: Dept. of Physiology, Univ. of Tübingen, Gmelinstr. 5, D-72076 Tübingen, Germany.
authors.forename: Teresa F
authors.initials: TF
authors.lastname: Ackermann
authors.forename: Krishna M
authors.initials: KM
authors.lastname: Boini
authors.forename: Harald
authors.initials: H
authors.lastname: Völkl
authors.forename: Madhuri
authors.initials: M
authors.lastname: Bhandaru
authors.forename: Petra M
authors.initials: PM
authors.lastname: Bareiss
authors.forename: Lothar
authors.initials: L
authors.lastname: Just
authors.forename: Volker
authors.initials: V
authors.lastname: Vallon
authors.forename: Kerstin
authors.initials: K
authors.lastname: Amann
authors.forename: Dietmar
authors.initials: D
authors.lastname: Kuhl
authors.forename: Yuxi
authors.initials: Y
authors.lastname: Feng
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hammes
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000042:Absorption; D000367:Age Factors; D000450:Aldosterone / Q000097:blood; D000818:Animals; D001692:Biological Transport; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight; D003404:Creatinine / Q000378:metabolism; D003920:Diabetes Mellitus / Q000097:blood / Q000378:metabolism* / Q000652:urine; D003928:Diabetic Nephropathies / Q000097:blood / Q000378:metabolism* / Q000652:urine; D004195:Disease Models, Animal; D004326:Drinking; D004435:Eating; D006029:Glycosuria / Q000097:blood / Q000378:metabolism* / Q000652:urine; D017874:Immediate-Early Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008564:Membrane Potentials; D051379:Mice; D018345:Mice, Knockout; D011188:Potassium / Q000097:blood / Q000652:urine; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012964:Sodium / Q000097:blood / Q000652:urine; D051269:Sodium-Glucose Transporter 1 / Q000378:metabolism; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D000450:Aldosterone; D001786:Blood Glucose; D003404:Creatinine; D017874:Immediate-Early Proteins; D011188:Potassium; D017346:Protein Serine-Threonine Kinases; D012964:Sodium; D051269:Sodium-Glucose Transporter 1; D000099184:Serum-Glucocorticoid Regulated Kinases; C495675:Slc5a1 protein, mouse