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.