Targeting 1,25(OH)2D-Mediated Calcium Absorption Machinery in Proximal Colon with Calcitriol Glycosides and Glucuronides

Publication date: Available online 24 December 2019Source: The Journal of Steroid Biochemistry and Molecular BiologyAuthor(s): H. Jiang, R.L. Horst, N.J. Koszewski, J.P. Goff, S. Christakos, J.C. FleetAbstractHigh intestinal calcium (Ca) absorption efficiency is associated with high peak bone mass in adolescents and reduced bone loss in adulthood. Transepithelial intestinal Ca absorption is mediated by 1,25-dihydroxyvitamin D (1,25(OH)2D, calcitriol) through the vitamin D receptor (VDR). Most research on Ca absorption focuses on the proximal small intestine but evidence shows that large intestine plays a crucial role in whole body Ca homeostasis. We directly assessed and compared Ca absorption capacity at the proximal colon and duodenum using in situ ligated loops (2 mM Ca, 10 min). In C57BL/6 J mice, the proximal colon (26.2 ± 3.7%) had comparable ability to absorb Ca as the duodenum (30.0 ± 6.7%). In VDR knockout (KO) mice, Ca absorption efficiency was reduced by 67% in duodenum and 48% in proximal colon. These data suggest that large intestine could be targeted to improve Ca absorption and protect bone in at risk-groups (e.g. bariatric patients). Glycoside forms of calcitriol found in Solanum Glaucophyllum (Sg) leaf are biologically inert but can be activated in the colon upon bacterial cleavage of the glycosides. We conducted a study to test whether Sg leaf, as well as a novel, synthetic 1,3-diglucuronide form of calcitriol (1,3-diG) could target the proxi...
Source: The Journal of Steroid Biochemistry and Molecular Biology - Category: Biochemistry Source Type: research