Invited ReviewVitamin D and diabetes: Where do we stand?
Introduction
Since many years, a role for vitamin D has been suggested outside bone and calcium metabolism, with beneficial effects suggested in defense against infectious agents, correlations with cancer and more recently also in prevention of diabetes.
Vitamin D can be obtained from food sources of vegetable origin (vitamin D2, also known as ergocalciferol) or animal (vitamin D3, also known as cholecalciferol). The best food sources are fatty fish and their oils. However, small amounts can also be found in butter and egg yolk. Cow's milk and human milk are relatively poor in vitamin D. Skim milk, in particular, often does not contain vitamin D. In many parts of the world, especially in North America, certain foods such as margarines, butter and cereals, are fortified with vitamin D. But the actual content of vitamin D is often quite different from the labeling standard and often insufficient to cover the daily needs [1]. Vitamin D3 itself is biologically inert and requires two successive hydroxylations, one in the liver, on the C25 position, the other in the kidney, in the α position on carbon one, to form the active hormone metabolite 1,25-dihydroxy vitamin D3 (1,25(OH)2D3). The hydroxylation enzymes belong to the family of cytochrome P450 (reviewed in [2]). Production of 1,25(OH)2D3 in the kidney is tightly regulated by several factors, including the level of parathyroid hormone, and the 1α-hydroxylase enzyme (CYP27B1) is subject to down-regulation by 1,25(OH)2D3 itself. The main site of production of 1,25(OH)2D3 by 1α-hydroxylation is the renal proximal tubule, but the presence of high levels of 1α-hydroxylase mRNA levels were also found in other tissues, human keratinocytes, dendritic cells and macrophages. This extra-renal production of 1,25(OH)2D3 is set in a completely different way. Production in macrophages, for example, is insensitive to stimulation by parathyroid hormone, but is directly activated by immune-stimulators such as IFN-γ and lipopolysaccharide (LPS) [3]. Circulating vitamin D metabolites are linked to a carrier protein, vitamin-D binding protein (DBP).
The optimal circulating levels of vitamin D remains subject of discussion [4], but levels of 25 (OH)D3 of 20–30 ng/mL (50–75 nmol/L) are considered adequate, whereas levels <20 ng/mL (<50 nmol/L) are viewed as deficient (reviewed in [4]).
Section snippets
Vitamin D and type 2 diabetes
T2D is a multifactorial disease triggered by an interplay of environmental factors and genetic predisposition. It has traditionally been considered a disease inflicting the elderly population. However, global alterations in lifestyle in combination with other risk factors like obesity and sedentarism have significantly increased the incidence among younger individuals and even children. Insulin resistance in target tissues such as skeletal muscle is essential for the pathogenesis of T2D. The
Vitamin D as an immune modulator in vitro and in experimental models of type 1 diabetes
Vitamin D exerts its action via the VDR, a nuclear receptor present in nearly all nucleated cells but with the highest concentration in the epithelial cells of the gut. The discovery that a wide variety of immune cells expressed the VDR as well as vitamin D-activating enzymes opened a whole new area for vitamin D as a natural therapeutic agent. However, the immune-modulatory effects of 1,25(OH)2D3 depend on supra-physiological concentrations that exceed systemic levels of this hormone.
Conclusions
The case for vitamin D as a player in the pathogenesis of both T2D and T1D is convincing: receptors for vitamin D are present in all tissues and organs involved in the diseases, the machinery for producing 1,25(OH)2D3 locally in islets, immune cells and other tissues involved is present, epidemiology relates levels of 25(OH)D3 to risk of disease, with vitamin D deficiency being associated with increased risk of both T2D and T1D, and finally, animal models of the diseases clearly demonstrate
Conflict of interest
The author have no conflict of interest.
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Odonto/Osteogenic Differentiation of Dental Pulp Stem Cells of Type 1 Diabetic Patients with Mineral Trioxide Aggregate/1α,25-Dihydroxyvitamin D3 Combination
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