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Akt/PKB‐sensitive proximal tubular glucose and phosphate transport
Author(s) -
Föller Michael,
Kempe Daniela S.,
Siraskar Gulab,
Fröhlich Henning,
Ackermann Teresa F.,
Siraskar Balasaheb,
Völkl Harald,
Judenhofer Martin,
Pichler Bernd,
Leavens Karla F.,
Birnbaum Morris J.,
Pearce David,
Lang Florian
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.606.5
Subject(s) - akt2 , endocrinology , medicine , protein kinase b , chemistry , glucose transporter , glucose uptake , glut1 , reabsorption , kidney , akt1 , biochemistry , biology , phosphorylation , insulin
Akt/PKB stimulates the glucose carrier GLUT4. Here we explored whether Akt directly regulates Na + ‐coupled transport of glucose (by SGLT1) or phosphate (by NaPiIIa). Immunohistochemistry showed that Akt2 is expressed in proximal renal tubules. According to dual electrode voltage clamp experiments the coexpression of Akt increased the glucose‐induced current in SGLT1‐expressing and the phosphate‐induced current in NapiIIa‐expressing Xenopus oocytes. Renal transport was further studied using Akt2 deficient ( akt2 −/− ) and wild type mice ( akt2 +/+ ). akt2 −/− mice suffered from glucosuria which was partially due to increased plasma glucose levels but was not observed in akt2 +/+ mice made similarly hyperglycemic as akt2 −/− mice by fructose feeding pointing to defective renal tubular glucose reabsorption. Glucose‐induced depolarization was significantly smaller in isolated perfused renal tubules from akt2 −/− than from akt2 +/+ mice. In addition, the phosphate clearance was higher in akt2 −/− than in akt2 +/+ mice despite a significantly decreased plasma PTH and enhanced 1,25‐dihydroxyvitamin D 3 concentration and a tendency of lower plasma phosphate. Bone density was significantly reduced in akt2 −/− mice. In conclusion, Akt plays a role in the regulation of renal glucose and phosphate transport contributing to the maintenance of phosphate balance and adequate mineralization of bone.