Abstract
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 ~20% of PDK-1 (pdk1^sup hm^) were compared with their wild-type littermates (pdk1^sup wt^). According to Ussing chamber experiments, electrogenic glucose transport was significantly smaller in the jejunum of pdk1^sup hm^ than of pdk1^sup wt^ mice. Similarly, proximal tubular electrogenic glucose transport in isolated, perfused renal tubule segments was decreased in pdk1^sup hm^ compared with pdk1^sup wt^ mice. Intraperitoneal injection of 3 g/kg body wt glucose resulted in a similar increase of plasma glucose concentration in pdk1^sup hm^ and in pdk1^sup wt^ mice but led to a higher increase of urinary glucose excretion in pdk1^sup hm^ 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. [PUBLICATION ABSTRACT]