Impaired intestinal and renal glucose transport in PDK-1 hypomorphic mice.
The phosphoinositide-dependent kinase-1 (PDK-1) activates the serum- and glucocorticoid-inducible kinase and protein kinase B isoforms, which, in turn, are known to stimulate the renal and intestinal Na+-dependent glucose transporter 1. The present study has been performed to explore the role of PDK-1 in electrogenic glucose transport in small intestine and proximal renal tubules. To this end, mice expressing approximately 20% of PDK-1 (pdk1hm) were compared with their wild-type littermates (pdk1wt). According to Ussing chamber experiments, electrogenic glucose transport was significantly smaller in the jejunum of pdk1hm than of pdk1wt mice. Similarly, proximal tubular electrogenic glucose transport in isolated, perfused renal tubule segments was decreased in pdk1hm compared with pdk1wt mice. Intraperitoneal injection of 3 g/kg body wt glucose resulted in a similar increase of plasma glucose concentration in pdk1hm and in pdk1wt mice but led to a higher increase of urinary glucose excretion in pdk1hm mice. In conclusion, reduction of functional PDK-1 leads to impairment of electrogenic intestinal glucose absorption and renal glucose reabsorption. The experiments disclose a novel element of glucose transport regulation in kidney and small intestine.
Artunc
Ferruh
F
Dept. of Physiology, Univ. of Tübingen, Gmelinstr. 5, D-72076 Tübingen, Germany.
Rexhepaj
Rexhep
R
Völkl
Harald
H
Grahammer
Florian
F
Remy
Christine
C
Sandulache
Diana
D
Nasir
Omaima
O
Wagner
Carsten A
CA
Alessi
Dario R
DR
Lang
Florian
F
D064413:3-Phosphoinositide-Dependent Protein Kinases; D000818:Animals; D001692:Biological Transport / Q000235:genetics / Q000502:physiology; D001786:Blood Glucose / Q000032:analysis; D004847:Epithelial Cells / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D006029:Glycosuria / Q000652:urine; D007421:Intestine, Small / Q000378:metabolism* / Q000503:physiopathology; D007687:Kidney Tubules, Proximal / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D008817:Mice, Mutant Strains; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D051269:Sodium-Glucose Transporter 1 / Q000235:genetics / Q000378:metabolism
D001786:Blood Glucose; C495675:Slc5a1 protein, mouse; D051269:Sodium-Glucose Transporter 1; D064413:3-Phosphoinositide-Dependent Protein Kinases; D017346:Protein Serine-Threonine Kinases; D005947:Glucose