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)

Aging is characterized, besides other changes, by a progressive increase in calcium content in the arterial wall, which is enhanced by diabetes mellitus, osteoporosis, arterial hypertension, and tabagism. As to tabagism, experiments in animals have shown that nicotine can increase calcium content of the arterial wall, and clinical studies have demonstrated that cigarette smoking induces peripheral vasoconstriction, with consequent increase in blood pressure levels. In order to study the role of calcium ions in the pathogenesis of the vasoconstrictive lesions caused by "acute" smoking, the author has studied the peripheral vascular effects of the calcium-channel antagonist nifedipine, a dihydropyridine derivative, and calcitonin, a hypocalcemizing hormone which possess vasoactive actions on 12 elderly regular smokers (mean age 65.8 years). The results demonstrated that both nifedipine (10 mg sublingually 20 min before smoking) and salmon calcitonin (100 MRC U/daily intramuscularly for three days) are able to prevent peripheral vasoconstriction evaluated by Doppler velocimetry, as well as the increase of blood pressure induced by smoking. On the basis of our results, the author proposes that cigarette smoking-induced vasoconstriction is a calcium-mediated process, which can be hindered by drugs with calcium antagonist action.
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PMID:Smoking, calcium, calcium antagonists, and aging. 222 75

Diabetes prone BB (DP BB) rats are known to develop insulin dependent diabetes mellitus. In addition, a number of other immune abnormalities have been observed, like severe T lymphopenia, lack of CD8+ T cells, and lack of RT6+ T cells. Here we report double-labelling studies of lymph node T cells using MRC OX-32 (CD45R), and demonstrate that this T cell subset is absent in young adult DP BB rats. Since both RT6 and MRC OX-32 antigens are only expressed by mature peripheral T cells, it is tempting to speculate that the peripheral T cell pool of DP BB rats consists only of immature peripheral T cells, i.e. recent thymic emigrants.
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PMID:Peripheral T cells in diabetes prone (DP) BB rats are CD45R-negative. 253 58

The present study was aimed at investigating the effect of calcitonin on plasma glucose, C-peptide, glucagon and growth hormone (GH) responses to arginine in insulin-dependent diabetic subjects. For this purpose, 6 insulin-requiring diabetics were submitted to an arginine tolerance test twice, in basal conditions and during the simultaneous infusion of salmon calcitonin (100 MRC) plus arginine in random order. Calcitonin caused a clear inhibition of the plasma glucose rise triggered by the amino acid, without significant modifications of the plasma C-peptide and glucagon responses. A significant rebound of plasma glucose was seen after calcitonin was stopped. Plasma GH rise following arginine administration was significantly inhibited by calcitonin. These findings suggest some positive interferences of calcitonin with the arginine-induced plasma glucose increase in insulin-dependent diabetes.
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PMID:Effect of Calcitonin on plasma glucose, C-peptide, glucagon and growth hormone responses to arginine in insulin-dependent diabetic subjects. 702 89

Granzyme A is a serine protease expressed by populations of human and mouse natural killer cells and activated CD4+ and CD8+ cytotoxic lymphocytes; its expression marks a subset of inflammatory cells in allografts, autoimmune diabetes, and a number of other inflammatory lesions. In order to describe more completely the correlation between granzyme A expression and the presence of in vivo cytolytic effects, we grafted allogeneic rat hearts with vascular anastomoses in a heterotopic location, and treated the hosts with either cyclosporine, anti-CD4 monoclonal antibody (MRC OX38), or no therapy. The grafts were evaluated by palpation for cardiac functions, by immunohistochemistry for CD4/CD8 expression, by hematoxylin-and-eosin staining for inflammatory infiltration, and by in situ hybridization for granzyme A expression. The appearance of granzyme A+ cells in untreated allografts preceded both functional and standard histopathological and immunohistochemical evidence of graft rejection by two days. In donor-recipient combinations where cyclosporine and anti-CD4 treatments allowed indefinite allograft survival, the allografts showed minimal numbers of granzyme A+ cells, whether cellular infiltrates developed or not. The number of granzyme A+ cells present in the cardiac allografts in treated and untreated animals correlated with either current or impending episodes of rejection. The early time course of granzyme A expression suggests that it can be used as an early and reliable marker of graft rejection.
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PMID:The use of granzyme A as a marker of heart transplant rejection in cyclosporine or anti-CD4 monoclonal antibody-treated rats. 842 39

Treatment of hypertension plays a key role in primary prevention of cerebrovascular attacks. Meta-analysis of 17 prospective studies of the treatment of hypertension proved that reduction of the systolic and diastolic blood pressure by 8-10/5-6 mmHg leads to a reduction of fatal and non-fatal cerebrovascular attacks by 40%. In the nineties a Swedish and British investigation of systolic-diastolic hypertension in elderly subjects-STOP and MRC-provided evidence of the great impact of treatment of hypertension in primary prevention of cerebrovascular attacks also in elderly hypertensive subjects (60-80 years). It is important to treat also in advanced age frequent isolated systolic hypertension as this improves markedly the prognosis of these patients and reduces the incidence of cerebrovascular and coronary complications, as was proved by the American study SHEP. The authors demonstrate that so far only the minority of hypertensive patients is treated effectively in this country and data from abroad indicate also that treatment of hypertension is lacking in the premorbid stage in more than half the patients with a cerebrovascular attack. The drugs of choice in treatment of hypertension in the elderly are small doses of thiazide diuretics and cardioselective beta-blockers or beta-blockers with ISA. By increasing the number of treated hypertensive patients, incl. elderly patients with a hypertension, and by increasing the effectiveness of treatment it is possible to achieve a decline of the cerebrovascular mortality; our objective must be a decline of the cerebrovascular mortality by more than 50%, similarly as it happened already in the USA. Conversely the importance of treatment of hypertension in secondary prevention of cerebrovascular attacks is controversial. The authors emphasize also the importance of abstinence from smoking as well as careful treatment of diabetes and hyperlipidaemia. Antiaggregation treatment has a greater impact in secondary prevention than treatment of hypertension. As regards the latter it should suffice to reduce the blood pressure to values of cca 150-160/90 -100 mmHg and not to normal values.
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PMID:[Treatment of hypertension in primary and secondary prevention of cerebrovascular stroke]. 892 16

Diuretics were used in most of the major trials that demonstrated that lowering the blood pressure reduced cardiovascular morbidity and mortality. Nevertheless in the second half of the eighties, there were misgivings about the widespread use of thiazide diuretics, driven in part by the relative failure of the large trials to reduce myocardial infarction-to the extent predicted by large scale epidemiological studies. There was much attention on metabolic side effects of thiazide diuretics including dyslipidaemia, glucose intolerance, hypokalaemia, hyperuricaemia, and then microalbuminuria particularly in diabetic subjects. These issues were current when JNC (IV) (1988) and the WHO-ISH guidelines (1989) were being written. Three major clinical trials SHEP, STOP and MRC published in the early nineties established that thiazide diuretics alone, or in combination with beta blockers, did reduce cardiovascular morbidity and mortality in elderly subjects with hypertension. All guidelines published since 1993 include diuretics among the first line drugs. Possibly the most important factor in the restoration of diuretics has been the use of progressively lower doses that minimise the metabolic side effects. Diuretics are effective as monotherapy in the treatment of mild essential hypertension and of isolated systolic hypertension in elderly subjects. They are very useful in combination with beta blockers or with ACE inhibitors. They should be avoided in patients with gout and should not be used as first line drugs in patients with diabetes. They should only be used with caution in young obese subjects with dyslipidaemia and increased risk of coronary artery disease, facing many decades of treatment for hypertension. However there is no doubt that diuretics are effective, cheap and have a central role in the control of hypertension in all communities around the world.
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PMID:[Role of diuretics in the treatment of hypertension: from large controlled trials to international guidelines]. 895 12

The records of 7086 patients reported to the MRC Glomerulonephritis Registry between 1978 and 1990 were examined; 1368 patients were aged > 60 years at the time of biopsy. In 1978 12% of patients aged > 60 years underwent biopsy, whereas in 1990 30% of patients were aged > 60 years. The most common reasons for biopsy were nephrotic syndrome (31%), acute renal failure (26%) and chronic renal failure (25%). In patients presenting with nephrotic syndrome, the most common histological appearance was membranous nephropathy (36.6%), minimal changes (11%) and amyloidosis (10.7%). Secondary nephrotic syndrome was associated with amyloidosis (32 patients), diabetes mellitus (11 patients) and carcinoma (10 patients). Glomerulonephritis in the elderly is not uncommon and the apparent increasing incidence is most likely due to an increased referral of patients for investigation rather than a true increase in the incidence of this condition.
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PMID:Glomerulonephritis in the elderly. 905 33

Lipids may adversely affect renal function. The recently published MRC/BHF Heart Protection Study (HPS) subgroup analysis showed that simvastatin significantly reduced the fall in glomerular filtration rate in high-risk patients with and without diabetes mellitus. These findings are in line with those of smaller earlier studies, including the GREek Atorvastatin and Coronary heart disease Evaluation (GREACE) Study. Lipid lowering trials need to consider that changes in renal function may occur. Renal and ischaemic heart disease may progress in parallel and statins may be beneficial to both organs.
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PMID:Statins and renal function in patients with diabetes mellitus. 1460 84

Rapidly accumulating evidence shows that common T-cell transcription factor (TCF)7L2 polymorphisms confer risk of type 2 diabetes through unknown mechanisms. We examined the association between four TCF7L2 single nucleotide polymorphisms (SNPs), including rs7903146, and measures of insulin sensitivity and insulin secretion in 1,697 Europid men and women of the population-based MRC (Medical Research Council)-Ely study. The T-(minor) allele of rs7903146 was strongly and positively associated with fasting proinsulin (P = 4.55 x 10(-9)) and 32,33 split proinsulin (P = 1.72 x 10(-4)) relative to total insulin levels; i.e., differences between T/T and C/C homozygotes amounted to 21.9 and 18.4% respectively. Notably, the insulin-to-glucose ratio (IGR) at 30-min oral glucose tolerance test (OGTT), a frequently used surrogate of first-phase insulin secretion, was not associated with the TCF7L2 SNP (P > 0.7). However, the insulin response (IGR) at 60-min OGTT was significantly lower in T-allele carriers (P = 3.5 x 10(-3)). The T-allele was also associated with higher A1C concentrations (P = 1.2 x 10(-2)) and reduced beta-cell function, assessed by homeostasis model assessment of beta-cell function (P = 2.8 x 10(-2)). Similar results were obtained for the other TCF7L2 SNPs. Of note, both major genes involved in proinsulin processing (PC1, PC2) contain TCF-binding sites in their promoters. Our findings suggest that the TCF7L2 risk allele may predispose to type 2 diabetes by impairing beta-cell proinsulin processing. The risk allele increases proinsulin levels and diminishes the 60-min but not 30-min insulin response during OGTT. The strong association between the TCF7L2 risk allele and fasting proinsulin but not insulin levels is notable, as, in this unselected and largely normoglycemic population, external influences on beta-cell stress are unlikely to be major factors influencing the efficiency of proinsulin processing.
Diabetes 2007 Jul
PMID:TCF7L2 polymorphisms modulate proinsulin levels and beta-cell function in a British Europid population. 1741 97

Circulat is a systemic standardized plant extract formulation that was developed for the prevention of severe manifestations of type 2 diabetes such as necrotic damage of the plantar foot. With the aim of revealing the molecular mechanisms underlying Circulat's biological activity, the effects of Circulat treatment on gene expression levels were examined in the cultured human fibroblast cell line MRC-5 using Affymetrix oligonucleotide microarrays. The analysis identified 187 genes, the expression levels of which underwent significant changes upon Circulat treatment. These include four genes (IL6, HMGA1, SLC19A2 and C4A) that have been implicated previously in the development of diabetes. A large proportion of the identified genes are involved in energy metabolism, protein synthesis, glucose metabolism and signaling pathways. Synergistic action of the Circulat components has also been revealed. Prospective applications of microarray analysis in phytopharmacology are discussed.
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PMID:Analysis of effects of the herbal preparation Circulat on gene expression levels in cultured human fibroblasts. 1751 33


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