Treatment with 10−8m 1,25-dihydroxyvitamin D3 for 24 h causes transcriptional activation of the human insulin receptor gene in U-937 human promonocytic cells. The activation seems to potentiate the response to insulin in terms of glucose oxidation. Wortmannin, a phosphatidylinositol 3-kinase inhibitor, causes a greater inhibition of insulin-stimulated glucose oxidation in 1,25-dihydroxyvitamin D3-treated cells than in untreated cells. This suggests a stimulation of phosphatidylinositol 3-kinase activity by 1,25-dihydroxyvitamin D3, which could mediate, at least in part, the potentiation of the insulin response. Copyright © 2002 John Wiley & Sons, Ltd.