The pleiotropic actions of vitamin D: Vitamin D and experimental asthma

Experimental allergic asthma was induced in VDR KO, WT, and 1,25(OH)2D3-treated WT mice. WT mice developed asth­ma, which was characterized by many inflammatory cells infil­trating the lungs. Lung histopathologic scores reflected the amount of epithelial hyperplasia and inflammation on a scale of 0 to 4 (maximum). The Th2 cell-driven disease experimental asthma failed to develop in VDR KO mice. 1,25(OH)2D3 treatment of WT control mice had no effect on asthma severity. VDR KO mice did develop antigen-specific Th2 cell responses in the periphery but failed to develop lung inflammation or air­way hyperresponsiveness. The absence of vitamin D sig­naling through VDRs protected these mice from developing ex­perimental asthma. The Th2 cell response develops in the ab­sence of VDRs; however, Th2 cells may not traffic to the lung and cause disease. It is also possible that epithelial cells in the lungs of VDR KO mice are unable to respond to an inflamma­tory challenge.

Vitamin D and diabetes

Several studies in rats and humans have demon­strated that vitamin D deficiency causes reduced insulin secre­tion, and that 1,25(OH)2D3 improves in p-cell function and con­sequently in glucose tolerance. In vitamin D-deficient rats, glucose tolerance and insulin secretion were improved with 1,25(OH)2D3 treatment. In gestational diabetes mel- litus, Rudnicki and Molsted-Petersen reported that the glucose level decreased after intravenous treatment with 1,25(OH)2D3. Vitamin D also corrects glucose intolerance and normalizes insulin sensitivity in uremic patients.

a) Type 1 diabetes mellitus

Some studies suggested that vitamin and its metabolites act in the regulation of the endocrine pancreas not only via the plasma calcium levels but also directly on the p- cells. 1,25(OH)2D3 may influence both endocrine and exocrine pancreatic function. The effects of 1,25(OH)2D3, a biolog­ically active metabolite of vitamin D, and its analogues have been examined regarding binding to nuclear VDR (nVDR) and membrane VDR (mVDR), through which they might induce ge- nomic and nongenomic responses respectively. In humans, Baumgartl et al. reported that serum 25OHD3 levels measured at matched time points throughout the year are lower in patients newly diagnosed with type 1 diabetes than in healthy controls. In 1999, the EURODIAB Substudy 2 Study Group studied the correlation between vitamin D supplements during the first year of life with the development of type 1 diabetes. They reported that vitamin D supplement during the first year of life is associated with a decreased risk of type 1 diabetes. In another study, Stene et al. investi­gated whether cod liver oil or vitamin D supplements taken ei­ther by the mother during pregnancy or by the child in the first year of life is associated with lower risk of type 1 diabetes in children. They found a lower risk of diabetes in children when mothers took cod liver oil during pregnancy. It was noted that newborn children of mothers who had taken cod liver oil during pregnancy had higher concentrations of 25(OH)D3 in the cord blood than children of mothers who had taken other vitamin D supplements during pregnancy. However, there was no significant protection from type 1 diabetes risks when infants were fed either cod liver oil or vitamin D supplements. They suggested that exposure in utero could be relevant for the de­velopment of type 1 diabetes. In addition, Hypponen et al. assessed the risk of type 1 diabetes and vitamin intake during infancy of 10.821 children in Oulu and Lappland of northern Finland. They reported that dietary vitamin supple­mentation is also associated with reduced risk of type 1 dia­betes.
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b) Type 2 diabetes mellitus

Vitamin D deficiency was linked to IGT (impaired glucose toler­ance) and type 2 diabetes in humans many years ago. These observations were confirmed in animal models, which demonstrated that pancreatic insulin secretion is inhibit­ed by vitamin D deficiency. Several reports have as­cribed an active role to vitamin D in the functional regulation of the endocrine pancreas, particularly the beta cells. Not only re­ceptors for 1,25(OH)2D3 are found in beta cells, but the effector part of the vitamin D pathway is also present in the form of vitamin D-dependent calcium-binding protein, also known as calbindin-D28. The expression of calbindin- D28k has been shown to protect beta cells from cytokine-medi- ated cell death. Several studies have demonstrated a link between VDR gene polymorphisms and type 2 diabetes, al­though the findings differ from one population to another. A study in Bangladeshi Asians demonstrated that the ApaI RFLP (Restriction Fragment Lenght Polymorphism) influences insulin secretion in response to glucose, while associations be­tween the VDR ApaI RFLP (restriction fragment lenght poly­morphism) and higher fasting plasma glucose levels and glu­cose intolerance were observed in a community-based study of older adults without known diabetes. More recently, genotyping for TaqI, ApaI, BsmI and FokI RFLPs revealed that the BsmI RFLP is associated with high fasting glucose levels in young males with low physical activity.

Category: Health

Tags: bone, pleiotropic actions, vitamin D

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