Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetic nephropathy (DN) is the most common renal complication of diabetes mellitus and a leading cause of end-stage renal disease. The renin-angiotensin system (RAS) is a major mediator of progressive renal injury in DN, and RAS inhibitors have been used as the mainstay treatment for DN. One major problem limiting the efficacy of the RAS inhibitors is the compensatory renin increase caused by disruption of renin feedback inhibition. Vitamin D negatively regulates the RAS by suppressing renin expression and thus plays a renoprotective role in DN. Diabetic vitamin D receptor-null mutant mice develop more severe renal injuries because of more robust RAS activation. Combination therapy with an RAS inhibitor and a vitamin D analogue markedly ameliorates renal injuries due to blockade of the compensatory renin increase by the analogue. These most recent data demonstrate that vitamin D and its analogues have renoprotective and therapeutic potentials in DN through targeting the RAS.
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PMID:Vitamin D and diabetic nephropathy. 1899 Mar 3

The role of vitamin D in maintaining bone health has been known for decades. Recently, however, the discovery that many tissues expressed the vitamin D receptor and were able to transform the 25-OH vitamin D into its most active metabolite, 1,25-(OH)(2) vitamin D, has led to a very promising future for this "old" molecule. Indeed, observational studies, and more and more interventional studies, are raising the importance of a significant vitamin D supplementation for not-only skeletal benefits. Among them, 25-OH vitamin D has been found to play an important role in prevention of cancers, auto-immune diseases, cardiovascular diseases, diabetes, and infections. Vitamin D deficiency, defined as serum 25-OH vitamin D levels <30 ng/mL, is very common in our population. The cost/benefit ratio and some recently published studies are clearly now in favor of a controlled and efficient vitamin D supplementation in these patients presenting a 25-OH vitamin D level <30 ng/mL. More attention should also be focused on pregnant and lactating women, as well as children and adolescents.
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PMID:Vitamin D: current status and perspectives. 1909 29

Type 2 diabetes mellitus (T2DM) is by far the most common type of diabetes and is characterized by insulin resistance and altered insulin secretion. Some genes, such as the vitamin D receptor gene (VDR, NM_001017535; GI: 7421), involved in its metabolic pathway have been regarded as good candidates for T2DM. In this study, we investigated whether there was an association of VDR: g.59979G>T or c.1025-49G>T (ApaIG>T) and g.60058T>C or c.1056T>C (TaqIT>C) polymorphisms in the 3' untranslated region of VDR with T2DM in a Turkish population. We collected blood samples from 241 individuals (72 patients with T2DM and 169 healthy individuals), and their DNA was isolated. Polymorphisms of the VDR were analyzed by DNA amplification with polymerase chain reaction and endonuclease digestion with ApaI and TaqI. Body mass index was higher in T2DM patients than in control individuals. However, the frequency of g.59979TT genotype in T2DM patients was not significantly increased compared to healthy subjects (37.5% vs. 36.1%, respectively). Although the VDR g.60058CC genotype in T2DM patients (19.4%) was higher than that in healthy individuals (11.2%), there was no significant difference. In the same way, there was no difference between the groups in allele frequencies. In conclusion, our study did not provide evidence for the association of two examined VDR polymorphisms with T2DM in a Turkish population.
J Diabetes Complications
PMID:Detection of VDR gene ApaI and TaqI polymorphisms in patients with type 2 diabetes mellitus using PCR-RFLP method in a Turkish population. 1918 74

The effect of the vitamin D receptor (VDR) gene polymorphisms on susceptibility to type 1 diabetes (T1DM) is heterogeneous. Genetic factors may also influence the residual beta-cell function. We studied the frequency of VDR FokI (rs10735810) and BsmI (rs154410) polymorphisms in T1DM and their relationship to beta-cell autoimmunity and residual beta-cell function. We genotyped 189 T1DM (diabetes duration, 7.1 +/- 5.4 years) and 194 controls (C) by restriction length polymorphism-polymerase chain reaction. GAD65Ab, IA2Ab, ionized calcium (iCa), HbA(1c)and fasting C-peptide (FCP) were evaluated. FCP values greater than 0.6 ng/ml were considered as residual beta-cell function. The BsmI was more frequent in the C (bb plus Bb 79.1 C vs. 66.1% T1DM, p = 0.006), and the FokI polymorphism frequencies were similar between T1DM and C. We did not observe differences in pancreatic autoantibody profiles according to VDR genotypes. We observed that T1DM with f allele tended to have lower residual pancreatic beta-cell function (5.8% ff and Ff vs. 14.3% FF, p = 0.074) with similar age, diabetes duration, AAb positivity, HbA(1c), and iCa. Age at diagnosis of T1DM with BsmI polymorphism tended to be greater (10.7 +/- 4.9 bb and Bb vs. 9.3 +/- 4.5 years BB, p = 0.06). In conclusion, the results of this study showed no relationship between VDR polymorphisms and beta-cell autoimmunity; however we observed a relationship with age and remaining beta-cell function in Brazilian individuals with T1DM. These data may contribute to understanding the heterogeneous relationship between genetic markers and clinical features observed in this disease.
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PMID:Prevalence of vitamin D receptor gene polymorphisms FokI and BsmI in Brazilian individuals with type 1 diabetes and their relation to beta-cell autoimmunity and to remaining beta-cell function. 1928 43

Exposure of the skin to sunlight is now considered the most important source of vitamin D in Western countries. It is presumed to contribute approximately two thirds of the total requirement, leaving the remaining one third to the few foods naturally rich in this vitamin. In the skin, vitamin D is synthesized as a cholesterol chain which undergoes structural modifications following exposure to UVB rays. Once produced in the skin or absorbed in the gut as cholecalciferol, vitamin D enters the blood to be transported by a specific vitamin D binding protein, which is synthesized in the liver and has a powerful buffering capacity. The transport system carries the metabolites to the sites of further activation (25-hydroxylation in the liver and 1alpha-hydroxylation in the kidney), ultimately resulting in the production of calcitriol. This last compound, now regarded as a hormone, circulates freely in minimal amounts and, compared with the other metabolites, shows the highest affinity for the vitamin D receptor (VDR). The mechanism of VDR activation is rather complex, resulting in either stimulation or inhibition of protein synthesis. Importantly, besides its presence in parathyroid, bone, kidney and intestine, this receptor has been demonstrated in several tissues, where its stimulation results in a reduced proliferation rate and increased differentiation. Accordingly, vitamin D is now regarded as a complex hormonal system, involved not only in the regulation of divalent ions and bone, but also in the proliferation and differentiation of numerous cell types with potential involvement in several diseases like cancer, immune diseases, diabetes, hypertension and heart failure.
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PMID:[Understanding the different functions of vitamin D]. 1964 19

A compromised vitamin D status, characterized by low 25-hydroxyvitamin D (25-(OH)D) serum levels, and a nutritional calcium deficit are widely encountered in European and North American countries, independent of age or gender. Both conditions are linked to the pathogenesis of many degenerative, malignant, inflammatory and metabolic diseases. Studies on tissue-specific expression and activity of vitamin D metabolizing enzymes, 25-(OH)D-1 alpha-hydroxylase and 25-(OH)D-24-hydroxylase, and of the extracellular calcium-sensing receptor (CaR) have led to the understanding of how, in non-renal tissues and cellular systems, locally produced 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) and extracellular Ca(2+) act jointly as key regulators of cellular proliferation, differentiation and function. Impairment of cooperative signalling from the 1,25-(OH)(2)D(3)-activated vitamin D receptor (VDR) and from the CaR in vitamin D and calcium insufficiency causes cellular dysfunction in many organs and biological systems, and, therefore, increases the risk of diseases, particularly of osteoporosis, colorectal and breast cancer, inflammatory bowel disease, insulin-dependent diabetes mellitus type I, metabolic syndrome, diabetes mellitus type II, hypertension and cardiovascular disease. Understanding the underlying molecular and cellular processes provides a rationale for advocating adequate intake of vitamin D and calcium in all populations, thereby preventing many chronic diseases worldwide.
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PMID:Vitamin D and calcium insufficiency-related chronic diseases: molecular and cellular pathophysiology. 1972 93

Vitamin D research is discussed in light of the hypothesis that the lower average levels of vitamin D frequently observed in autoimmune disease are not a sign of deficiency. Instead, it is proposed that the lower levels result from chronic infection with intracellular bacteria that dysregulate vitamin D metabolism by causing vitamin D receptor (VDR) dysfunction within phagocytes. The VDR dysfunction causes a decline in innate immune function that causes susceptibility to additional infections that contribute to disease progression. Evidence has been accumulating that indicates that a number of autoimmune diseases can be reversed by gradually restoring VDR function with the VDR agonist olmesartan and subinhibitory dosages of certain bacteriostatic antibiotics. Diseases showing favorable responses to treatment so far include systemic lupus erythematosis, rheumatoid arthritis, scleroderma, sarcoidosis, Sjogren's syndrome, autoimmune thyroid disease, psoriasis, ankylosing spondylitis, Reiter's syndrome, type I and II diabetes mellitus, and uveitis. Disease reversal using this approach requires limitation of vitamin D in order to avoid contributing to dysfunction of nuclear receptors and subsequent negative consequences for immune and endocrine function. Immunopathological reactions accompanying bacterial cell death require a gradual elimination of pathogens over several years. Practical and theoretical implications are discussed, along with the compatibility of this model with current research.
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PMID:Reversing bacteria-induced vitamin D receptor dysfunction is key to autoimmune disease. 1975 26

Vitamin D deficiency is an increasingly described phenomenon worldwide, with well-known impacts on calcium metabolism and bone health. Vitamin D has also been associated with chronic health problems such as bowel and colonic cancer, arthritis, diabetes and cardiovascular disease. In recent decades, there has been increased awareness of the impact of vitamin D on muscle morphology and function, but this is not well recognized in the Sports Medicine literature. In the early 20th century, athletes and coaches felt that ultraviolet rays had a positive impact on athletic performance, and increasingly, evidence is accumulating to support this view. Both cross-sectional and longitudinal studies allude to a functional role for vitamin D in muscle and more recently the discovery of the vitamin D receptor in muscle tissue provides a mechanistic understanding of the function of vitamin D within muscle. The identification of broad genomic and non-genomic roles for vitamin D within skeletal muscle has highlighted the potential impact vitamin D deficiency may have on both under-performance and the risk of injury in athletes. This review describes the current understanding of the role vitamin D plays within skeletal muscle tissue.
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PMID:Vitamin D and human skeletal muscle. 1980 97

Vitamin D exerts its physiological functions on calcium and bone metabolism in humans through the active metabolite 1,25-dihydroxyvitamin D3(1,25(OH)2D3). The other spectrum of vitamin D activities includes important effects on cellular proliferation, differentiation and the immune system. These effects are mediated through the intracellularly located vitamin D receptor (VDR). VDR is a member of the steroid, estrogen and retinoid receptor gene family of proteins that mediate transcriptional activities of the respective ligands. The VDR complex binds in the nucleus to the vitamin D responsive element on the gene. Several polymorphisms of the vitamin D receptor (VDR) gene have been described including FokI in exon 2, BsmI and ApaI in intron 8 and TaqI in exon 9. Alterations in vitamin D-1,25 (OH)2D3 levels and polymorphisms of VDR gene have been shown to be associated with several malignant or autoimmune diseases such as sclerosis multiplex, breast cancer, diabetes mellitus, malignant melanoma, and psoriasis vulgaris. The effects of VDR gene polymorphisms including immunomodulation, stimulation of cellular differentiation and inhibition of proliferation make it a possible candidate for therapy of psoriasis as well as for the psoriasis gene modification. The objective of this article is to present the state-of-the-art in the VDR gene polymorphism research in psoriasis vulgaris.
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PMID:Vitamin D endocrine system and psoriasis vulgaris--review of the literature. 1981 18

The calcineurin inhibitors-cyclosporine and tacrolimus-are the mainstay of immunosuppressive therapy in solid organ transplantation. These drugs produce severe adverse drug effects (ADEs) such as nephrotoxicity, posttransplantation diabetes mellitus, and hypertension. Accumulated evidence suggests that the development of type 2 diabetes, hypertension, and renal failure may be associated with specific DNA genotypes. In this review, the genes involved with the development of these disease processes are compared with those implicated in calcineurin inhibitor-induced ADEs. The renin-angiotensin system genes, cytokine-encoding genes, and plasminogen activator inhibitor type 1 genes have been implicated in calcineurin inhibitor-induced nephrotoxicity, as well as in development of renal failure. A number of genes are implicated in contributing to diabetes, and these include the vitamin D receptor gene, VDR; hepatocyte nuclear factor genes, HNF; transcription factor 7-like 2 gene, TCF7L2; angiotensin-converting enzyme gene, ACE; cytokines; peroxisome proliferator-activated receptor gamma gene, PPARG; and others. Studies have suggested that the VDR, PPARG, HNF1A, and adenosine 5'-triphosphate-binding cassette ABCC8 (which encodes the sulfonylurea receptor) genes are associated with calcineurin inhibitor-induced diabetes. The genes encoding for the angiotensin-converting enzyme, endothelial constitutive nitric oxide synthase, and cytochrome P450 3A isoenzyme have been involved in the development of hypertension and in calcineurin inhibitor-induced hypertension. The genetic study of disease states can be the stepping stones for thoroughly understanding the genetic basis of ADEs. Gene polymorphisms are implicated in the development of diseases and corresponding disease-like ADEs. The disease-associated genes provide candidate genes for exploring ADEs and may provide genomic biomarkers for assessing the risk for developing severe calcineurin inhibitor-related ADEs as well as for developing preventive strategies.
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PMID:Understanding the genetic basis for adverse drug effects: the calcineurin inhibitors. 2009 93


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