Decreased intestinal glucose transport in the sgk3-knockout mouse.
Xenopus oocyte coexpression experiments revealed the capacity of the serum- and glucocorticoid-inducible kinase isoform 3 (SGK3) to up-regulate a variety of transport systems including the sodium-dependent glucose transporter SGLT1. The present study explored the functional significance of SGK3-dependent regulation of intestinal transport. To this end, experiments were performed in gene targeted mice lacking functional sgk3 (sgk3(-/-)) and their wild type littermates (sgk3(+/+)). Oral food intake and fecal dry weight were significantly larger in sgk3(-/-) than in sgk3(+/+) mice. Glucose-induced current (I(g)) in Ussing chamber as a measure of Na(+) coupled glucose transport was significantly smaller in sgk3(-/-) than in sgk3(+/+) mouse jejunal segments. Fasting plasma glucose concentrations were significantly lower in sgk3(-/-) than in sgk3(+/+) mice. Intestinal electrogenic transport of phenylalanine, cysteine, glutamine and proline were not significantly different between sgk3(-/-) and sgk3(+/+) mice. In conclusion, SGK3 is required for adequate intestinal Na(+) coupled glucose transport and impaired glucose absorption may contribute to delayed growth and decreased plasma glucose concentrations of SGK3 deficient mice. The hypoglycemia might lead to enhanced food intake to compensate for impaired intestinal absorption.
Sandu
Ciprian
C
Department of Physiology I, University of Tübingen, Gmelinstr. 5, 72076 Tuebingen, Germany.
Rexhepaj
Rexhep
R
Grahammer
Florian
F
McCormick
James A
JA
Henke
Guido
G
Palmada
Monica
M
Nammi
Srinivas
S
Lang
Undine
U
Metzger
Marco
M
Just
Lothar
L
Skutella
Thomas
T
Dawson
Kevin
K
Wang
Jian
J
Pearce
David
D
Lang
Florian
F
D000818:Animals; D004435:Eating; D005243:Feces; D017874:Immediate-Early Proteins / Q000235:genetics / Q000502:physiology*; D007408:Intestinal Absorption / Q000502:physiology*; D007583:Jejunum / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D051269:Sodium-Glucose Transporter 1 / Q000502:physiology*; D000099184:Serum-Glucocorticoid Regulated Kinases
D017874:Immediate-Early Proteins; D017346:Protein Serine-Threonine Kinases; D051269:Sodium-Glucose Transporter 1; D000099184:Serum-Glucocorticoid Regulated Kinases