Impaired intestinal and renal glucose transport in PDK-1 hypomorphic mice

Impaired intestinal and renal glucose transport in PDK-1 hypomorphic mice. Am J Physiol Regul Integr Comp Physiol 291: R1533-R1538, 2006. First published June 1, 2006; doi: 10.1152/ajpregu.00024.2006.-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 similar to 20% of PDK-1 (pdk1(hm)) were compared with their wild-type littermates (pdk1(wt)). According to Ussing chamber experiments, electrogenic glucose transport was significantly smaller in the jejunum of pdk1(hm) than of pdk1(wt) mice. Similarly, proximal tubular electrogenic glucose transport in isolated, perfused renal tubule segments was decreased in pdk1(hm) compared with pdk1(wt) mice. Intraperitoneal injection of 3 g/kg body wt glucose resulted in a similar increase of plasma glucose concentration in pdk1(hm) and in pdk1(wt) mice but led to a higher increase of urinary glucose excretion in pdk1(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.