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This Article Full Text Full Text (PDF) All Versions of this Article: 296/4/F859    most recent 90238.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Ackermann, T. F. Articles by Lang, F. Search for Related Content PubMed PubMed Citation Articles by Ackermann, T. F. Articles by Lang, F.

SGK1-sensitive renal tubular glucose reabsorption in diabetes

¹Department of Physiology, University of Tübingen, Tübingen, Germany; ²Department of Physiology and Medical Physics, Innsbruck Medical University, Innsbruck, Austria; ³Department of Anatomy, University of Tübingen, Tübingen, Germany; ⁴Departments of Medicine and Pharmacology, University of California, San Diego and Veterans Affairs San Diego Healthcare System, San Diego, California; ⁵Department of Pathology, University of Erlangen, Erlangen; ⁶Department of Biology, Chemistry, and Pharmacy, Free University Berlin, Berlin; ⁷5th Medical Clinic, Faculty of Clinical Medicine, University of Heidelberg, Mannheim, Germany; and ⁸Department of Nephrology, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan, China

Submitted 4 April 2008 ; accepted in final form 16 January 2009

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 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.

serum- and glucocorticoid-inducible kinase 1; diabetic nephropathy; glucose transport; sodium-glucose cotransporter; kidney