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)

The most important side effects of oral contraceptives (OCs) and their incidence, together with advice and monitoring of the patient at risk, are pointed out. There is a mild increase in blood pressure in longterm contraceptive use caused by increased angiotensinogen production by the liver. It is significant only for women with a history of familial hypertension, diabetes mellitus, or pre-eclampsia. Smoking increases this risk. Urinary tract infections are 25-50% more frequent in pill users. Glucose tolerance is slightly decreased. Contraceptives' diabetogenic effect is higher in women with hereditary tendency for diabetes, latent diabetes, and/or obesity. They are contraindicated in latent diabetes. Findings are contradictory in their effects on cholesterol and triglyceride serum level, but the pill is contraindicated in lipid metabolism disorders. There is an increased incidence in cholecystitis and cholelithiasis in pill-users (70-80 additional cases/100,000 user years). Liver diseases, intrahepatic cholestasis, occur rarely and benign liver tumors have not conclusively been proved to be caused by the pill. A variety of laboratory findings have been related to contraceptive use and drug interactions occur with barbiturates, rifampicin, hydantoin, and phenylbutazone. Blood coagulation is increased, partially by increased production of various blood coagulation factors; but more importantly, by a decreased synthesis of antithrombin III, a natural protective mechanism against intravascular coagulation. This increases thrombosis risk. Risk doubles with simultaneous cigarette smoking. Various epidemiological studies indicate a 5-10 fold increase in thromboembolism and thrombophlebitis, deep vein thrombosis, and pulmonary embolism. There is a correlation between contraceptive use and cerebrovascular disorders and myocardial infarction. This risk increases with age and years of pill use. The pill is contraindicated with symptoms of thrombophlebitis and thromboembolism, sickle cell anemia, proposed surgery, and longterm immobilization. Overall risk factors are not too high. Recommendations for rational pill use related to age are given and further contraindications are mentioned.
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PMID:[Adverse effects of oral contraceptives]. 55 52

Renin substrate (angiotensinogen) in unfractionated human plasma has been shown to exist in multiple forms by DEAE-cellulose chromatography and isoelectric focusing. Two major and 5 to 6 minor peaks were resolved by using a descending pH gradient elution from DEAE-cellulose columns. The two predominant forms were eluted at or near pH 4.8 and 4.4 and usually accounted for 40--50% of the recovered substrate activity. The elution pH values of the various forms were nearly constant among plasmas from normal males and females and in diabetes, early and late pregnancy and estrogen substitution therapy. The relative distribution of components was not affected by prior freezing of the plasma or by dialysis against the column buffer. Eight renin substrate forms were clearly resolved during isoelectric focusing of plasma from a woman on estrogen substitution therapy. Four of these focused at pH 4.79, 4.88, 4.94 and 5.02 in 1% (w/v) ampholytes pH 3.5--5 and were nearly equal in substrate amount. Together these 4 forms constituted 66% of the total recovered activity. A similar pattern but with decreased amounts of each form of substrate was obtained with normal plasma.
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PMID:Multiple forms of renin substrate in human plasma. 62 80

Genetic factors contribute significantly to the development of diabetic nephropathy in patients with insulin-dependent diabetes mellitus. This report discusses some models of diabetic nephropathy that incorporate genetic susceptibility and presents strategies for identifying the responsible genes. To identify variation at a locus, newly developed methods are discussed that employ denaturing gradient gel electrophoresis to study sequence differences in both polymerase chain reaction-amplified DNA fragments and genomic DNA. These techniques are illustrated with studies of the angiotensinogen gene and the insulin receptor gene. In preliminary data from a comparison between individuals with and without diabetic nephropathy, no DNA sequence difference in that part of the angiotensinogen gene that codes for angiotensin I was found. However, with a probe corresponding to exons 7 and 8 of the insulin receptor gene and denaturing gradient gel electrophoresis of Rsal digestions of genomic DNA, different distributions of a DNA polymorphism were found in patients with fast as compared with slowly progressing nephropathy. The interpretation of this finding and the need for further studies are discussed. In conclusion, the advent of methods of molecular genetics makes possible studies on genetic determinants of diabetic nephropathy. However, more clinical and epidemiologic data are needed to find out how many genes are involved and how they interact with exposure to diabetes. Foremost, DNA from families with two or more siblings with diabetic nephropathy must be collected to permit the necessary genetic studies.
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PMID:Molecular genetic approaches to the identification of genes involved in the development of nephropathy in insulin-dependent diabetes mellitus. 145 65

The renin-angiotensin system may play a role in the initiation and progression of diabetic kidney disease. In this study, the local intrarenal renin-angiotensin system was examined in streptozotocin-treated rats maintained moderately hyperglycemic by daily low-dose insulin injection. Four weeks after induction of diabetes, plasma renin activity was significantly lower in the diabetic compared to a non-diabetic control group (diabetes: 2.30 +/- 0.30 vs. control: 6.93 +/- 1.36 ng Al/ml/hr; P less than 0.01). Renal tissue renin content (diabetes: 1.81 +/- 0.46 vs. control: 2.05 +/- 0.27 micrograms Al/mg protein/hr; P less than 0.05) and renal renin mRNA (diabetes: 2.32 +/- 0.16 vs. control: 1.89 +/- 0.12 pg/micrograms RNA; P = NS) were not different between diabetic and control rats. Renal and liver angiotensinogen mRNA were lower in the diabetic group. Glomerular renin mRNA was not different between the diabetic and sham group. The dissociation between systemic renin activity (a decrease), and in renal renin content or mRNA in the diabetic rats (no change), suggests a post-translational alteration in renin processing and/or renin secretion.
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PMID:Renin and angiotensinogen gene expression in experimental diabetes mellitus. 151 2

It is well known that diabetes mellitus is often associated with hypertension. We previously reported the unresponsiveness of renin release to volume depletion with impaired renal prostaglandin E2 synthesis in rats with streptozotocin-induced diabetes. However, we have found that BioBreeding Worcester rats, spontaneously susceptible to diabetes mellitus either before or after the onset of diabetes, showed a pronounced fourfold to ninefold increase in plasma renin activity in comparison with control Wistar rats. Furthermore, these rats developed mild hypertension as high as 134 mm Hg after the age of 90 days. The hyperreninemia responded to 1-week sodium loading or restriction; the blood pressure increased during sodium loading. Oral administration of captopril (30 mg/kg) for 1 week resulted in a large blood pressure decrease (-47.1 +/- 5.9 mm Hg, n = 10) in comparison with controls (-17.0 +/- 4.7 mm Hg, n = 12). Vascular response to angiotensin II was also attenuated. Plasma angiotensin II levels were 5.7-fold higher and associated with a 1.5-fold increase of plasma aldosterone concentration compared with control rats, whereas angiotensinogen-plasma concentrations were lower than in control rats. The renal renin content determined enzymatically or histochemically was more enhanced in BioBreeding Worcester rats than in control rats, but the renal renin messenger RNA levels did not differ. These results suggest that the strain-specific hyperreninemia in BioBreeding Worcester rats might be due to posttranscriptional abnormalities of renal renin synthesis. Further work is needed to elucidate the specific mechanism or mechanisms responsible.
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PMID:Hyperreninemia due to increased renal renin synthesis in BioBreeding Worcester rats. 169 97

The expression of renin and angiotensinogen genes and their proteins were studied during the progression of diabetes using adult BioBreeding spontaneously diabetic rats at 1 day and 2-12 months of diabetes. The number of renin-stained cells per juxtaglomerular apparatus was determined by immunocytochemistry. Initially, at 2 months of diabetes the number of renin-stained cells per juxtaglomerular apparatus increased significantly (p less than 0.0001, 2 months versus resistant groups) and was followed by a decrease in the number and intensity of renin-stained cells after 12 months of diabetes (p = 0.007, 2 months versus 12 months). A significant negative correlation was observed between the number of renin-containing cells and the duration of diabetes (r = 0.99, p = 0.014). Immunoreactive angiotensinogen was restricted to the proximal tubule and appeared increased after 4 and 8 months of diabetes as compared with the 2- and 12-month diabetic groups. Renin messenger RNA (mRNA) levels increased with the onset of diabetes and decreased markedly during chronic diabetes. At 1 day of diabetes, renin mRNA levels were 700% higher than at 12 months of diabetes. Angiotensinogen mRNA levels were unchanged. We conclude that diabetes results in an initial increase in renin gene expression, and as the duration of diabetes lengthens, there is a progressive decrease in renin gene expression and in the number of cells containing renin. These findings suggest that as the duration of diabetes and the age of the animal lengthens, there is a decrease in the number of cells expressing the renin gene.
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PMID:Renin and angiotensinogen expression during the evolution of diabetes. 173 Apr 42

To determine if insulin has the ability to regulate components of the renin-angiotensin system, renin and angiotensinogen mRNA and plasma concentrations were determined in 4-wk streptozotocin (STZ)-diabetic rats. In another group of STZ-diabetic rats, replacement insulin therapy was given over the 4-wk period, and the above parameters were examined. In STZ-diabetic rats, there was a significant regression of white adipose tissue that was accompanied by an increase in the yield of RNA obtained. Changes in white adipose tissue were reversed by insulin replacement therapy in STZ-diabetic rats. There were no changes in brown adipose tissue weight or RNA yield in STZ-diabetic rats. Plasma renin activity (PRA) was significantly decreased in STZ-diabetic rats; however, plasma angiotensinogen concentration was not significantly affected by diabetes. PRA was restored to control levels in STZ-diabetic rats with insulin replacement. Kidney renin mRNA as well as liver, epididymal, and interscapular fat angiotensinogen mRNA were significantly decreased in STZ-diabetic rats. Renin and angiotensinogen mRNA were not significantly different from control in all tissues examined in STZ-diabetic rats with insulin replacement therapy. Results from this study suggest a downregulation of the renin-angiotensin system in 4-wk STZ-diabetic rats at the level of mRNA expression that is restored by replacement therapy with insulin; therefore, insulin may directly or indirectly regulate the renin-angiotensin system.
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PMID:Downregulation of the renin-angiotensin system in streptozotocin-diabetic rats. 173 40

Sensitivity and accuracy are essential features of an assay of plasma renin activity (PRA) because the normal concentration of PRA is only 1 pmol/L, and subnormal concentrations have diagnostic relevance. Conditions for blood collection need to be standardized but the conditions are not difficult for outpatients. For routine diagnostic purposes blood should be collected from ambulatory (ideally, untreated) patients on moderate sodium intake. To avoid irreversible cryoactivation of plasma prorenin (which is present in 10-fold greater concentrations than renin), samples should be processed at room temperature and stored completely frozen. Cryoactivation occurs when plasma is liquid at temperatures less than 6 degrees C. PRA is commonly measured with an enzyme kinetic assay in which angiotensin I (Ang I) is formed by the reaction of plasma renin with endogenous renin substrate (angiotensinogen). The Ang I so formed is measured by RIA; results are expressed as an hourly rate (micrograms/L formed per hour). This method, which is provided by most commercial kits, has the potential for unlimited sensitivity because the step for Ang I generation can be prolonged as long as necessary, so that enough Ang I forms to be measured accurately. Unfortunately, that sensitivity is not always exploited. Dilution of plasma during pH adjustment should be kept to a minimum. The Ang I generation step should last at least 3 h. The step should last 18 h for samples with PRA less than 1.0 micrograms/L per hour, to eliminate the errors inherent in the measurement and subtraction of immunoreactive Ang I in the untreated plasma (blank subtraction). These changes actually simplify PRA measurements because they eliminate the need for ice in the clinic and reduce by almost half the number of samples to be assayed by RIA. I also describe the method for measurement of plasma prorenin, which may be an important marker for patients with diabetes mellitus who subsequently develop vascular complications.
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PMID:Plasma renin activity and plasma prorenin assays. 191 95

During the past decade, experimental and clinical evidence has indicated an important role for the renin-angiotensin system in the progressive destruction of nephrons in a wide variety of chronic renal diseases. Studies have indicated that in the subtotally nephrectomized rat model of progressive glomerulosclerosis, in experimental diabetes mellitus, in the chronic phase of puromycin aminonucleoside-induced nephrotic syndrome and in Heymann's nephritis, angiotensin-converting enzyme (ACE) inhibitors dramatically preserve both nephron structure and function. Clinical studies have similarly noted that chronic administration of ACE inhibitors inhibits progression of renal failure in type I diabetes and type II diabetes as well as primary glomerulopathies, sickle cell nephropathy, systemic lupus erythematosis, chronic pyelonephritis and adult polycystic kidney disease. Current evidence suggests that the beneficial effect of ACE inhibitors is primarily due to inhibition of angiotensin II production, and there is strong suggestive evidence for increases in local intrarenal activation of the renin-angiotensin system in these conditions. In obstructive uropathy, activation of the renin-angiotensin system has also been shown to be an important aspect of the early functional changes and may be of importance in the subsequent generation of interstitial fibrosis. In the obstructed kidney, renin and angiotensinogen production increase and type I angiotensin receptors decrease. Inhibitors of angiotensin II production and angiotensin II action partially reverse the vasoconstriction and the reduced renal blood flow, and abolish the changes in expression of AT1 MRNA induced by obstruction. Studies suggest that the angiotensin-mediated increases in tubulointerstitial fibrosis may be mediated by increased production of transforming growth factor-beta.
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PMID:Angiotensin II-mediated renal injury. 756 81

Combined molecular and epidemiological studies are advancing our understanding of the genetic basis of multifactorial diseases. Several of the results obtained during the past year highlight methodological issues associated with these approaches. For example, the affected sib-pair method has been applied successfully to detect linkage between the angiotensinogen gene and susceptibility to hypertension, and a large multi-centre epidemiological study has demonstrated association of a polymorphism of the angiotensin-converting enzyme gene with increased risk of myocardial infarction. The study of Mendelian forms of multifactorial diseases has also led to many new results. These include the characterization of mutations in the glucokinase gene in maturity onset diabetes of the young, localization to chromosome 2 of a gene involved in familial colon cancer, and localization to chromosome 19 of a gene responsible for hemiplegic migraine. New insights have been provided into the genetics of multifactorial disorders such as diabetes and hypertension through the study of animal models. Localization of susceptibility loci in such models has recently led to the identification of new candidate genes that may be implicated in disease.
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PMID:Genetic approaches to common diseases. 776 64


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