SGK1-sensitive renal tubular glucose reabsorption in diabetes.
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SGK1-sensitive renal tubular glucose reabsorption in diabetes. / Ackermann, Teresa F; Boini, Krishna M; Völkl, Harald; Bhandaru, Madhuri; Bareiss, Petra M; Just, Lothar; Vallon, Volker; Amann, Kerstin; Kuhl, Dietmar; Feng, Yuxi; Hammes, Hans-Peter; Lang, Florian.
In: AM J PHYSIOL-RENAL, Vol. 296, No. 4, 4, 2009, p. 859-866.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - SGK1-sensitive renal tubular glucose reabsorption in diabetes.
AU - Ackermann, Teresa F
AU - Boini, Krishna M
AU - Völkl, Harald
AU - Bhandaru, Madhuri
AU - Bareiss, Petra M
AU - Just, Lothar
AU - Vallon, Volker
AU - Amann, Kerstin
AU - Kuhl, Dietmar
AU - Feng, Yuxi
AU - Hammes, Hans-Peter
AU - Lang, Florian
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 296
SP - 859
EP - 866
JO - AM J PHYSIOL-RENAL
JF - AM J PHYSIOL-RENAL
SN - 1931-857X
IS - 4
M1 - 4
ER -