SGK1-dependent stimulation of intestinal SGLT1 activity by vitamin D.

The serum- and glucocorticoid-inducible kinase SGK1 has previously been shown to mediate the glucocorticoid-dependent stimulation of several intestinal transport systems including the electrogenic glucose transporter SGLT1. In squamous carcinoma cells, SGK1 expression is stimulated by 1,25(OH)2D3, the biologically active metabolite of vitamin D. The present study explored whether vitamin D influences the intestinal SGLT1 activity. Jejunal SGLT1 activity was determined by Ussing chamber experiments. Under a normal diet, the electrogenic glucose transport was similar in SGK1 knockout (sgk1 ( -/- )) and wild type mice (sgk1 ( +/+ )). Following a vitamin D-rich diet (14 days 10,000 I.U. vitamin D), the SGK1 transcript levels as well as the SGLT1 protein abundance were increased in sgk1(+/+) mice. Moreover, SGLT1 activity was increased in sgk1(+/+) mice but not in sgk1(-/-) mice following a vitamin D-rich diet. Furthermore, an oral glucose load was followed by an increase in the plasma glucose concentration to significantly higher values in sgk1(+/+) mice treated with a vitamin D-rich diet than in untreated sgk1(+/+) mice. In conclusion, vitamin D treatment upregulates the expression of SGK1, which in turn enhances SGLT1 activity.