Metabolic functions of vitamin D
The principal function of vitamin D is to maintain the plasma concentration of calcium; calcitriol achieves this in three ways:
● increased intestinal absorption of calcium
● reduced excretion of calcium by stimulating resorp-tion in the distal renal tubules (due to increased calbindin D synthesis)
● mobilization of bone mineral.
There is a growing body of evidence that low vitamin D status (but not such a degree of deficiency as to disturb calcium homeostasis) is associated with impaired glucose tolerance, insulin resistance and non-insulin dependent diabetes mellitus, as well as obesity and the low grade chronic inflammation asso-ciated with (especially abdominal) obesity. There is also evidence poor vitamin D status is a factor in the etiology of some cancers. Calcitriol has a variety of permissive or modulatory effects; it is a necessary, but not sufficient, factor, in:
● synthesis and secretion of insulin, parathyroid, and thyroid hormones;
● inhibition of production of interleukin by activated
T-lymphocytes and of immunoglobulin by acti-vated B-lymphocytes;
●differentiation of monocyte precursor cells;
●modulation of cell differentiation, proliferation and apoptosis.
In most of its actions, the role of calcitriol seems to be in the induction or maintenance of synthesis of calcium binding proteins, and the physiological effects are secondary to changes in intracellular calcium concentrations.
Calcitriol acts like a steroid hormone, binding to a nuclear receptor protein, commonly as a heterodimer with the RXR (vitamin A) receptor, then binding to hormone response elements on DNA and modifying the expression of one or more genes.
The best-studied actions of vitamin D are in the intestinal mucosa, where the intracellular calcium binding protein induced by vitamin D is essential for the absorption of calcium from the diet. Vitamin D also acts to increase the transport of calcium across the mucosal membrane by recruiting calcium trans-port proteins to the cell surface.
Calcitriol also raises plasma calcium by stimulating the mobilization of calcium from bone. It achieves this by activating osteoclast cells. However, it acts later to stimulate the laying down of new bone to replace the loss, by stimulating the differentiation and recruit-ment of osteoblasts.