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)

Vitamin D analogs exert a preventative effect on experimental diabetes, but whether or not they are able to halt progress of established diabetes is not yet known. Moreover, it is widely accepted that diabetes may induce osteoporosis, but the efficacy of vitamin D on diabetic osteoporosis is not clear. In order to help clarify these issues, we have tested the efficacy of calcitriol streptozotocin-induced diabetes. Streptozotocin (60 mg/Kg body weight) was injected in 3-month-old Wistar rats, randomly distributed into two groups: vehicle (olive oil) treated diabetic rats (D) and diabetic rats treated with 1.25-(OH)2D3 250 mg, three times a week (DT). Control animals (C) were treated with vehicle alone. The experiment lasted 8 weeks. The histology of the pancreata was evaluated. Blood glucose and calcium and phosphate in serum and urine were measured. Finally, bone mineral density (BMD) of tibia and lumbar vertebrae were evaluated. After 8 weeks, diabetes persisted in 85% of the diabetic rats (D group), but in only 45% of vitamin D-treated group (DT). At the end of the experiment, DT animals were separated into two groups, those still remaining diabetic (DT-NR) and reversed animals (DT-R). Moreover, bone loss was observed in diabetic animals (D), whereas BMD of DT-R rats showed similar values to those of controls (C). Our results suggest that 1.25(OH)2D3 improves diabetes and, as such, may recover BMD in streptozotocin-induced diabetic rats.
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PMID:Calcitriol improves streptozotocin-induced diabetes and recovers bone mineral density in diabetic rats. 1565 97

Dialysis, in its routine 3 x week manifestation, undoubtedly is life saving. The therapy is limited by a number of factors that persist despite the development of safe machines and highly efficient dialyzers. The turnover of known, and very likely, many unknown uremic toxins, is rapid so that 3 x week dialysis is accompanied by relatively high levels of these substances. Only the lower part of the range of molecular weights of those putative uremic toxins, which are small proteins, are removed by current therapies. For substances such as phosphorus, long dialysis is successful in removing the excess retained dietary phosphorus, perhaps the only proven uremic toxin. The difficulty of achieving a normal extracellular volume is probably a major factor in the progression and poor outcomes of cardiovascular disease despite the potential improvement with management of hyperlipidemia, inflammation, potential arrhythmias, and cardiac failure due to other pathogenetic mechanisms. New developments in understanding of Vitamin D metabolism, Ca receptor inhibitor drugs, and control of hyperphosphatemia may reduce the problems of kidney bone disease and the adverse cardiovascular effect of calcium phosphorus disposition. Dialysis more frequent than 3 x week is already routinely, if only infrequently, used to deal with the very large volume or overhydrated patient. However, daily dialysis--whether short or long-is now beginning as a therapy with a large randomized NIH trial in the offing. Currently, the net growth of dialysis is approximately 4% a year, but it would not be surprising if there were a gradual increase in growth rates as CKD patients live longer due to control of cardiac disease. Eventually, the treatment of early kidney disease should reduce the dialysis population, particularly if diabetes can be better controlled or even prevented. The dialysis aspect of nephrology as a profession for physicians, nurses, and technicians appears to be on a long course with increasing demand and the need for applying what is already known, while awaiting new technical developments. Wearable artificial kidneys, involving the application of technology and use of new materials, are currently being investigated. The presence of nephrologists during the actual dialysis treatment is certainly not as evident as it was in the past. Reimbursement methodology has ensured at least a minimum of documented visits by nephrologists or nurse practitioners to the dialysis patient during treatment. It is controversial as to the value of this, but evidence has been presented that certain outcomes, such as use of appropriate dialysis dose and blood chemistries, are improved by more frequent visits. The present is over.
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PMID:Technology: kidneys--the present of dialysis. 1567 76

To address whether diabetes enhances lipid peroxidation and attenuates nitric oxide (NO) generation resulting in tissue complications, we measured oxysterols and NO metabolites (NOx) in the tissues of diabetic Wistar rats. After 4 weeks of streptozotocin injection (STZ, 80 mg/kg, i.p.), we measured 7 alpha- and 7 beta-hydroperoxycholest-5-en-3 beta-ol (7 alpha-OOH and 7 beta-OOH), 7 alpha- and 7 beta-hydroxycholesterol (7 alpha-OH and 7 beta-OH) and 7-ketocholesterol (7-keto) by HPLC in the kidneys, heart, and liver. All the oxysterols were much higher in the diabetic than in sham rats, while the extent of the increase was higher in the order of the kidney, heart, and liver. Together with high blood urea nitrogen, the data indicate that the kidney is the predominant target of early diabetic complications. Plasma NOx were decreased by 20% in the STZ rats. The enhanced oxidative stress in diabetes would increase oxysterols by peroxidation, while superoxide is known to reduce NO by reaction to form another potent oxidant peroxynitrite.
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PMID:Oxysterols increase in diabetic rats. 1578 34

The relationship between autoimmune diabetes or type 1 diabetes mellitus and vitamin D has been reported in the literature. Many factors, environmental and genetic, have been known, as risk factors, to cause both type 1 diabetes and vitamin D deficiency. Vitamin D treatment has improved or prevented type 1 diabetes mellitus in animals and humans. Vitamin D also has been known to protect from autoimmune diseases in animal models. Therefore, it would be interesting to review the role of vitamin D in type 1 diabetes mellitus.
Diabetes Metab Res Rev
PMID:The role of vitamin D in protecting type 1 diabetes mellitus. 1585 46

Vitamin D is taken for granted and is not appreciated for its importance in overall health and well-being. Vitamin D, known as the sunshine vitamin, is appreciated as being important for the prevention of rickets in children. It is now recognized that vitamin D is important for not only the growing skeleton, but for the maintenance of a healthy musculoskeletal system throughout life. Vitamin D deficiency in adults precipitates and exacerbates osteoporosis and causes the painful bone disease osteomalacia. The revelation that vitamin D is biologically inactive and requires sequential hydroxylations in the liver and kidney to form 1,25-dihydroxyvitamin D helps explain why patients with renal failure are often resistant to vitamin D and suffer from secondary hyperparathyroidism and renal osteodystrophy. In addition to its role in maintaining calcium and phosphorus homeostasis, vitamin D is now being recognized as important for maintaining maximum muscle strength and for the prevention of many chronic diseases, including type I diabetes, multiple sclerosis, rheumatoid arthritis, hypertension, cardiovascular heart disease, and many common cancers. Vitamin D status is best determined by the measurement of circulating levels of 25-hydroxyvitamin D. Vigilance for maintaining a 25-hydroxyvitamin D level of at least 20 ng/ml and preferably 30-50 ng/ml has important benefits for both healthy children and adults, as well as children and adults suffering from chronic kidney disease.
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PMID:Vitamin D for health and in chronic kidney disease. 1607 48

Vitamin D is very important for overall health and wellbeing. A major source of vitamin D comes from exposure to sunlight. Measurement of 25-hydroxyvitamin D in the blood and not 1,25-dihydroxyvitamin D is used to determine vitamin D status. A blood level of 25-hydroxyvitamin D of at least 20 ng/mL is considered to be vitamin D sufficient. Vitamin D deficiency increases the risk of many common cancers, multiple sclerosis, rheumatoid arthritis, hypertension, cardiovascular heart disease, and type I diabetes.
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PMID:Vitamin D: important for prevention of osteoporosis, cardiovascular heart disease, type 1 diabetes, autoimmune diseases, and some cancers. 1629 17

The Vitamin D endocrine system regulates multiple aspects of calcium metabolism and cellular differentiation and replication in the immune system, endocrine pancreas, liver, skeletal muscles and adipocytes. It plays an important role in glucose homeostasis, notably, in the mechanism of insulin release. Actions of vitamin D are mediated by the binding of 1, 25-(OH)2D3 to a specific cytosolic/nuclear vitamin D receptor (VDR), a member of the steroid/thyroid hormone receptor superfamily. Several frequent polymorphisms are found in the VDR gene and were reported to be associated with a variety of physiological and pathological phenotypes in many populations. In this paper, we will review the evidences suggesting associations of allelic variations in the VDR gene and phenotypes related to body weight, glucose homeostasis, diabetes and its vascular complications.
Diabetes Metab 2005 Sep
PMID:Vitamin D endocrine system and the genetic susceptibility to diabetes, obesity and vascular disease. A review of evidence. 1636 93

Vitamin D insufficiency is more prevalent among African Americans (blacks) than other Americans and, in North America, most young, healthy blacks do not achieve optimal 25-hydroxyvitamin D [25(OH)D] concentrations at any time of year. This is primarily due to the fact that pigmentation reduces vitamin D production in the skin. Also, from about puberty and onward, median vitamin D intakes of American blacks are below recommended intakes in every age group, with or without the inclusion of vitamin D from supplements. Despite their low 25(OH)D levels, blacks have lower rates of osteoporotic fractures. This may result in part from bone-protective adaptations that include an intestinal resistance to the actions of 1,25(OH)2D and a skeletal resistance to the actions of parathyroid hormone (PTH). However, these mechanisms may not fully mitigate the harmful skeletal effects of low 25(OH)D and elevated PTH in blacks, at least among older individuals. Furthermore, it is becoming increasingly apparent that vitamin D protects against other chronic conditions, including cardiovascular disease, diabetes, and some cancers, all of which are as prevalent or more prevalent among blacks than whites. Clinicians and educators should be encouraged to promote improved vitamin D status among blacks (and others) because of the low risk and low cost of vitamin D supplementation and its potentially broad health benefits.
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PMID:Vitamin D and African Americans. 1654 93

Vitamin D3 is synthesized in the skin during summer under the influence of ultraviolet light of the sun, or it is obtained from food, especially fatty fish. After hydroxylation in the liver into 25-hydroxyvitamin D (25(OH)D) and kidney into 1,25-dihydroxyvitamin D (1,25(OH)2D), the active metabolite can enter the cell, bind to the vitamin D-receptor and subsequently to a responsive gene such as that of calcium binding protein. After transcription and translation the protein is formed, e.g. osteocalcin or calcium binding protein. The calcium binding protein mediates calcium absorption from the gut. The production of 1,25(OH)2D is stimulated by parathyroid hormone (PTH) and decreased by calcium. Risk factors for vitamin D deficiency are premature birth, skin pigmentation, low sunshine exposure, obesity, malabsorption and advanced age. Risk groups are immigrants and the elderly. Vitamin D status is dependent upon sunshine exposure but within Europe, serum 25(OH)D levels are higher in Northern than in Southern European countries. Severe vitamin D deficiency causes rickets or osteomalacia, where the new bone, the osteoid, is not mineralized. Less severe vitamin D deficiency causes an increase of serum PTH leading to bone resorption, osteoporosis and fractures. A negative relationship exists between serum 25(OH)D and serum PTH. The threshold of serum 25(OH)D, where serum PTH starts to rise is about 75nmol/l according to most surveys. Vitamin D supplementation to vitamin D-deficient elderly suppresses serum PTH, increases bone mineral density and may decrease fracture incidence especially in nursing home residents. The effects of 1,25(OH)2D and the vitamin D receptor have been investigated in patients with genetic defects of vitamin D metabolism and in knock-out mouse models. These experiments have demonstrated that for active calcium absorption, longitudinal bone growth and the activity of osteoblasts and osteoclasts both 1,25(OH)2D and the vitamin D receptor are essential. On the other side, bone mineralization can occur by high ambient calcium concentration, so by high doses of oral calcium or calcium infusion. The active metabolite 1,25(OH)2D has its effects through the vitamin D receptor leading to gene expression, e.g. the calcium binding protein or osteocalcin or through a plasma membrane receptor and second messengers such as cyclic AMP. The latter responses are very rapid and include the effects on the pancreas, vascular smooth muscle and monocytes. Muscle cells contain vitamin D receptor and several studies have demonstrated that serum 25(OH)D is related to physical performance. The active metabolite 1,25(OH)2D has an antiproliferative effect and downregulates inflammatory markers. Extrarenal synthesis of 1,25(OH)2D occurs under the influence of cytokines and is important for the paracrine regulation of cell differentiation and function. This may explain that vitamin D deficiency can play a role in the pathogenesis of auto-immune diseases such as multiple sclerosis and diabetes type 1, and cancer. In conclusion, the active metabolite 1,25(OH)2D has pleiotropic effects through the vitamin D receptor and vitamin D responsive elements of many genes and on the other side rapid non-genomic effects through a membrane receptor and second messengers. Active calcium absorption from the gut depends on adequate formation of 1,25(OH)2D and an intact vitamin D receptor. Bone mineralization mainly depends on ambient calcium concentration. Vitamin D metabolites may play a role in the prevention of auto-immune disease and cancer.
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PMID:Vitamin D physiology. 1656 71

Vitamin D functions to regulate calcium homeostasis in intestine, kidney, and bone. Vitamin D deficiency during bone development causes rickets and in adults vitamin D deficiency, which has been shown to be common in the elderly population, can cause secondary hyperparathyroidism that can result in osteomalacia and increased risk of fracture. Recent evidence has suggested that vitamin D can have numerous other physiological functions including protection against certain autoimmune diseases, such as diabetes and multiple sclerosis and inhibition of proliferation of a number of malignant cells including breast and prostate cancer cells. Exactly how vitamin D affects numerous different systems is a subject of continuing investigation. This article will review new developments related to the function and regulation of vitamin D target proteins in classic vitamin D target tissues that have provided novel insight into the mechanism of vitamin D action.
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PMID:New insights into the mechanisms involved in the pleiotropic actions of 1,25dihydroxyvitamin D3. 1683 19


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