Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Calcitonin concentration (CT) was measured in 52 children with insulin-dependent diabetes (IDDM). All the patients studied were divided into three groups. The first group consisted of children with freshly diagnosed diabetes remaining in the condition of ketonemic acidosis. The second group was composed of children with the well controlled diabetes during the first two years od duration of the disease. The third group included the patients with poorly controlled diabetes of the duration longer than ten years having the accompanying vascular complications. The control values were determined in children without metabolic disturbances of either diabetic or other origin. CT concentration was significantly elevated both in the patients of the first group and those of the third group. In the second group the concentration of this hormone was close to normal. It is known that calcitonin participates in the homeostasis of calcium and is an important regulator of insulin secretion. The results obtained suggest that calcitonin may play a role both in the pathogenesis of diabetes and in developing of diabetic osteopenia.
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PMID:[Level of calcitonin in blood serum of children with insulin dependent diabetes]. 136 94

Ion channels in beta cells regulate electrical and secretory activity in response to metabolic, pharmacologic, or neural signals by controlling the permeability to K+ and Ca2+. The ATP-sensitive K+ channels act as a switch that responds to fuel secretagogues or sulfonylureas to initiate depolarization. This depolarization opens voltage-dependent calcium channels (VDCC) to increase the amplitude of free cytosolic Ca2+ levels ([Ca2+]i), which triggers exocytosis. Acetyl choline and vasopressin (VP) both potentiate the acute effects of glucose on insulin secretion by generating inositol 1,4,5-trisphosphate to release intracellular Ca2+; VP also potentiates sustained insulin secretion by effects on depolarization. In contrast, inhibitors of insulin secretion decrease [Ca2+]i by either hyperpolarizing the beta cell or by receptor-mediated, G-protein-coupled effects to decrease VDCC activity. Repolarization is initiated by voltage- and Ca(2+)-activated K+ channels. A human insulinoma voltage-dependent K+ channel cDNA was recently cloned and two types of alpha 1 subunits of the VDCC have been identified in insulin-secreting cell lines. Determining how ion channels regulate insulin secretion in normal and diabetic beta cells should provide pathophysiologic insight into the beta cell signal transduction defect characteristic of non-insulin dependent diabetes (NIDDM).
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PMID:The role of ion channels in insulin secretion. 138 42

Renal failure was found in a five-year-old patient who had been treated with insulin since he was diagnosed as having insulin dependent diabetes mellitus (IDDM) at 3 years of age. Laboratory data showed that his renal failure was caused by a renal tubular dysfunction. The autopsy findings of his pancreas were compatible with those of IDDM. The kidneys were atrophied with an innumerable number of crystals in the proximal tubuli. Staining by Kossa indicated that the crystals contained calcium salt. The calcium content of his kidneys was significantly higher than that of control. The nephrocalcinosis seems to be caused by hypercalciuria associated with IDDM.
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PMID:Insulin dependent diabetes mellitus accompanied by nephrocalcinosis and renal failure. 144 54

The clinical linkage of hypertensive cardiovascular disease, left ventricular hypertrophy, and accelerated atherosclerosis with a spectrum of metabolic disturbances including peripheral insulin resistance, hyperinsulinemia, obesity, and frank non-insulin dependent diabetes mellitus, has been increasingly appreciated. However, the underlying biologic basis mediating this clinical association remains unclear. Nuclear magnetic resonance techniques have been used to measure various intracellular ion species in human erythrocytes and have found that common, shared intracellular abnormalities of cytosolic free calcium, free magnesium, and pH occur in each of these clinical syndromes. Specifically, essential hypertension is characterized by higher fasting free cytosolic calcium concentrations and reciprocally lower intracellular free magnesium and pH levels compared with those of normotensive control subjects. Furthermore, for all subjects, free calcium and free magnesium levels were closely related both to the left ventricular mass and to the degree of insulin resistance present. Moreover, these same intracellular ionic lesions were found in normotensive obese and/or non-insulin diabetic individuals. Last, evidence has recently been provided that the cardiovascular consequences of increased dietary sugar and salt intake may well be determined by their concurrent influence on cellular ion metabolism. These data led to a hypothesis for a central role for altered cellular ion homeostasis in mediating the clinical linkage of cardiovascular and metabolic disease. According to this ionic hypothesis, essential hypertension, non-insulin dependent diabetes, and their frequently associated features of obesity, left ventricular hypertrophy, and accelerated atherosclerosis all derive from and reflect different clinical manifestations of the same underlying cellular lesion, characterized at least in part by elevated cytosolic free calcium and suppressed free magnesium levels.
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PMID:Cellular ions in hypertension, insulin resistance, obesity, and diabetes: a unifying theme. 145 64

The influence of insulin on plasma and bone mineral homeostasis was studied in the BB rat model, which develops an autoimmune form of diabetes at the age of about 100 days. Untreated diabetes of short duration resulted in hypercalciuria and intestinal calcium malabsorption despite increased free concentrations of serum 1,25-dihydroxyvitamin D. The concentrations of two vitamin D-dependent calcium-binding proteins were also decreased: a low duodenal calbindin-D 9K concentration corresponding to the low intestinal active calcium absorption and a low serum osteocalcin concentration, corresponding to a low bone formation and highly correlated with serum IGF-I concentration. Indeed, on bone histology a very low number of osteoblasts and low osteoblast activity (osteoid formation and mineral apposition rate) were observed. Similar abnormalities persisted in rats with long-standing diabetes resulting in markedly decreased bone mass and increased brittleness of bone. Diabetes therefore resulted in low-turnover osteoporosis. Several hormones (testosterone, growth hormone and 1,25-dihydroxyvitamin D) and growth factors (IGF-I and its binding proteins) with known effects on bone were markedly decreased in diabetic rats. A continuous infusion of testosterone, GH or 1,25-(OH)2D3 for 14 d by miniosmotic pumps could not improve the biochemical or histomorphometric abnormalities. Insulin infusion for 2 weeks, however, rapidly increased and overcorrected the number of osteoblasts, normalized serum osteocalcin and IGF-I concentrations but could not yet normalize bone mineralization. Continuous infusion of IGF-I alone did not improve the osteoblast number of osteocalcin but markedly stimulated bone mineralization. From these data we can conclude that both insulin and IGF-I are potent bone growth factors but with different mode of action. In human type 1 diabetes, a similar decrease in serum osteocalcin and IGF-I was observed. A reduction of regional bone mass, both in long and trabecular bones, is frequently observed in human diabetes. Cumulative data from case control studies indicate that the life-time fracture risk is increased in diabetes.
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PMID:Diabetic bone disease. Low turnover osteoporosis related to decreased IGF-I production. 146 60

Diabetic renal disease is a clinical syndrome in which proteinuria is followed by the development of renal failure, and is commonly associated with the concomitant development of hypertension. In insulin-dependent diabetic (IDDM) patients, hypertension often first appears in the microalbuminuric phase of diabetic nephropathy whereas in non-insulin-dependent diabetic (NIDDM) patients, hypertension often antecedes nephropathy and may precede the diagnosis of diabetes. Antihypertensive regimens including diuretics, vasodilators such as hydralazine, beta-blockers and ACE inhibitors reduce proteinuria and delay the decline in renal function in IDDM patients with established nephropathy. No such data are as yet available for calcium antagonists. In microalbuminuric diabetic patients with hypertension, conventional antihypertensive agents, ACE inhibitors and calcium antagonists have been shown to decrease urinary albumin excretion. In the diabetic patient with normal blood pressure and microalbuminuria, there is much less information. It appears likely that ACE inhibitors reduce or retard the rate of increase in albuminuria in these patients. The effect on ultimately delaying or preventing renal failure remains unknown although the preliminary evidence is encouraging. Data on calcium antagonists remain inconclusive with some reports suggesting an increase in proteinuria with the dihydropyridine calcium antagonists. However, a recent longer term study suggested that nifedipine may prevent the rise in albuminuria which is generally observed in the untreated normotensive microalbuminuric subject.
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PMID:The management of diabetic proteinuria. Which antihypertensive agent? 150 44

The ability to stimulate and induce responses of T cells is influenced by their age and state of differentiation. We have examined the response upon restimulation of T cells expanded in IL-2. Our results demonstrate that large numbers of T cells, which after activation react by secreting IL-2, can be obtained from small numbers of PBL. In this study T cells were grown in IL-2 and, after 12-14 days, IL-2 was withdrawn in order to deprive them of growth factors. Our findings showed that after resting for 48 hours without IL-2, IL-2-dependent cells reverted to small lymphocytes, ceased to incorporate 3H-TdR, and had no mRNA for activation antigens such as Tac or IL-2. The cells could be reactivated to proliferate by stimulation with a calcium ionophore ionomycin and phorbol dibutyrate (PdB). Cells from insulin dependent diabetes mellitus patients with a defined immunoregulatory defect were then studied. Our results demonstrated that the IL-2 expanded cells evidenced the immunoregulatory defect for IL-2 synthesis that we had initially defined using virgin T cells from peripheral blood. These results demonstrate that studies of immune function can be undertaken in donors from whom limited numbers of peripheral blood lymphocytes are available using primed cells which have been allowed to dedifferentiate.
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PMID:The response pattern of human T cells to stimulation following expansion in IL-2. 172 96

Kidney disease is a primary cause of morbidity and mortality in diabetic patients. Factors that predetermine development of nephropathy remain unknown. Poor glycemic control, insulin requirement, duration of diabetes and family history of hypertension appear to be associated with an increased risk. Arterial hypertension, which is twice as common in diabetic patients as in the normal population, accelerates the progression of diabetic nephropathy. The pathophysiologic mechanisms responsible for hypertension appear to be different in IDDM and NIDDM. In IDDM, hypertension occurs usually as a consequence of diabetic renal disease. Conversely, the pathogenesis in NIDDM appears to be multifactorial. In either condition, aggressive blood pressure control is the single most important intervention proven to retard the progression of nephropathy. A stepped-care approach similar to that for essential hypertension with slight modifications is indicated in the treatment of the hypertensive diabetic patient with nephropathy. Nonpharmacological therapy, including dietary protein restriction, should be used as first step. Selection of the ideal antihypertensive must be based not only on efficacy but also on its side effect profile. Angiotensin converting enzyme inhibitors and calcium antagonists have a low incidence of side effects and do not induce metabolic disturbances. Therefore, they are the agents of choice for patients who do not respond to nonpharmacological therapy alone. Thiazide diuretics and beta-blockers should be used as first line therapy only for specific indications. Antihypertensive therapy combined with good glycemic control and dietary protein restriction constitute the standard of care for diabetic patients with hypertension and renal disease.
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PMID:Hypertension and kidney disease of diabetes mellitus. 176 55

To assess the changes of calcium metabolism and osteopathy in patients with diabetes. Serum Ca, P, AKP, PTH, CT, plasma fasting blood glucose (FBG) and HbA1 as well as X-ray film of the lumbar spine were measured in 30 diabetes patients; 11 were IDDM and 19 were NIDDM as compared to controls matched for age and sex. There were no significant differences in Ca, P, and CT values in serum between the IDDM and NIDDM patients and controls, whereas the serum levels of PTH and AKP were significant increased in IDDM patients. The incidence of osteoporosis which was shown by X-ray film in NIDDM patients was higher than in those of controls. No correlation between PTH value and osteoporosis or clinical control of diabetes was observed.
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PMID:Calcium metabolism and osteopathy in diabetes mellitus. 195 49

The development of IDDM results from the destruction of pancreatic beta cells. Genetic factors, various immune system alterations, and environmental factors have been studied as the possible causes of IDDM. The concordance rate for developing IDDM between monozygotic twins approaches 50%, suggesting that genetic factors are necessary, but nongenetic factors such as various immune system alterations and environmental factors also influence the clinical expression of genetic susceptibility. Environmental factors (e.g., viruses, chemicals, and diet) affecting the induction of diabetes may act as primary injurious agents which damage pancreatic beta cells or as triggering agents of autoimmunity. Certain viruses including EMC-D and Mengo virus 2T can directly infect pancreatic beta cells and replicate in the cells. The replication of viruses in the beta cells results in the destruction of the cells within 3 days, and the infected mice develop a diabeteslike syndrome in 3-4 days without the involvement of autoimmunity. In contrast, rubella virus appears to be somewhat weakly associated with autoimmune IDDM in hamsters. In addition, endogenous retrovirus expressed in pancreatic beta cells is clearly associated with the development of insulitis and diabetes in NOD mice. In man, there appears to be no correlation between the detection of islet cell autoantibodies and anti-Coxsackie B viral antibodies in newly diagnosed IDDM. In contrast, persistent infection of CMV and rubella virus appears to be associated with the presence of autoantibodies in newly diagnosed IDDM patients. It is particularly noteworthy that human CMV can induce islet cell autoantibodies that react specifically with a 38 kDa islet cell protein which may represent islet cell-specific antigens in a proportion of CMV-associated IDDM cases. These observations suggest that the association of diabetes with Coxsackie B viruses might be due to cytolytic infection of the beta cells with no link to autoimmunity, while both rubella virus and CMV are probably associated with autoimmune IDDM. A number of structurally diverse chemicals including alloxan, streptozotocin, chlorozotocin, Vacor, and cyproheptadine are diabetogenic mainly in rodents and sometimes in man. Possible mechanisms for beta cell destruction by these chemicals include (a) generation of oxygen free radicals and alteration of endogenous scavengers of these reactive species; (b) breakage of DNA and a consequent increase in the activity of poly-ADP-ribose synthetase, an enzyme depleting nicotinamide adenine dinucleotide in beta cells; and (c) inhibition of active calcium transport and calmodulin-activated protein kinase activity. (ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The role of viruses and environmental factors in the induction of diabetes. 207 86


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