The phosphoinositide dependent kinase PDK1 activates the serum

and glucocorticoid-inducible kinase isoforms SGK1, SGK2 and SGK3 and protein kinase B which in turn are known to stimulate SGLT1. The present study has been performed to explore the role of PDK1 in electrogenic glucose transport in small intestine and proximal renal tubules. To this end, mice expressing 10-25% of PDK1 (pdk1hm) were compared to their wild type littermates (pdk1wt). According to Ussing chamber experiments electrogenic glucose transport was significantly (p<0.05) smaller in jejunum of pdk1hm (-501±74mA/cm ²) than of pdk1wt mice (-831±117mA/cm ²). Similarly, proximal tubular electrogenic transport in isolated perfused renal tubule segments was decreased in pdk1hm as compared to pdk1wt mice. Intraperitoneal injection of 3 g/kg bw glucose led to a similar increase of plasma glucose concentration in pdk1hm and pdk1wt mice but led to a more marked glucosuria in pdk1hm mice (13.8±4.6 mg glc/mg creatinine) than in pdk1wt mice (2.4±0.8 mg glc/mg creatinine). In conclusion, reduction of functional PDK1 leads to impairment of electrogenic intestinal glucose absorption and renal glucose reabsorption. The experiments disclose a novel mechanism of glucose transport regulation.