Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.15.1 (ACE)
18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The enzymes delta5-3beta-hydroxysteroid dehydrogenase delta5-3beta-HSD) and glucose-6-phosphate dehydrogenase (G-6-PDH) were demonstrated histochemically in the adrenal cortex of female rat. The activities of these enzymes were increased significantly in the alloxan-treated rats kept in LD (light: darkness) cycles of 10:14 h. Continuous light exposure to diabetic animals appeared to decrease delta5-3beta-HSD and g-6-PDH in comparison to the diabetic rats kept in 10 h illumination. The evidence indicates that suppression of adrenal steroidogenesis in diabetic rats after exposure to continuous light is due to the alteration of pentose phosphate pathway.
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PMID:Adrenal dehydrogenases in alloxan diabetic rats following continuous exposure to light. 60 81

Evidence is presented for regulation by insulin of pyruvate dehydrogenase (pdh) interconversion in rat heart muscle in vivo and in vitro. In the alloxan diabetic rat the active (dephospho) enzyme amounted only to 12% of total PDH and was restored to 42% by insulin. Antilipolytic treatment of the dibetic animals was ineffective, indicating that the action of insulin was independent of a lowering of plasma non-esterified fatty acid concentration. On perfusion of isolated hearts from diabetic rats in the presence of glucose the proportion of pyruvate dehydrogenase in the active form remained low but was fully restored upon addition of insulin (2mU/ml) to the medium. No effect of insulin was obtained in the absence of glucose. The correlation between the rate of pyruvate decarboxylation in the perfused heart and of pyruvate dehydrogenase activity, in vitro, suggests that in the diabetic heart the entry of pyruvate into the citric acid cycle is largely controlled by covalent modification of the pyruvate dehydrogenase complex rather than by feedback inhibition. The possible role of insulin therein is discussed.
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PMID:The effect of insulin on pyruvate dehydrogenase interconversion in heart muscle of alloxan-diabetic rats. 63 58

Infusion of bradykinin (1 microgram/min) or saline vehicle for 30 minutes into alloxan-diabetic rats produced no change in the very high levels of blood glucose. Furthermore, intravenous injection of captopril (3 mg/Kg body weight) into the diabetic rats did not result in a significant change of glucose concentrations over a period of 60 minutes. However, infusion of bradykinin 15 minutes after intravenous injection of captopril resulted in a marked decrease of glucose levels (p less than 0.01, compared to pretreatment) by 20 minutes after the start of the infusion. Thus, the captopril potentiated the effect of the kinin, possibly by inhibition of kininase II. Using a spectrophotometric assay with Bz-Gly-Gly-Gly as substrate insulin was shown to be an inhibitor of kininase II purified from hog lungs with an I50 of 1.6 X 10(-5)M compared to captopril with I50 of 2.2 X 10(-9)M. Furthermore, it was found that in vivo infusion of as little as 50 mU insulin over a period of 30 minutes, a dose that by itself was ineffective, potentiated the glucose-lowering activity of a bradykinin infusion in alloxanized rats. Interestingly, the infusion of insulin 15 minutes after injection of captopril, at doses of each compound which alone were inactive, did produce a significant fall (p less than 0.005) in glucose concentrations. Overall, the results show that captopril, insulin and bradykinin can interact to promote a reduction in blood glucose of alloxan-diabetic rats.
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PMID:Studies of the effects of insulin, bradykinin, and captopril on blood glucose levels of alloxan-diabetic rats. 302 79

A defect in the renin-angiotensin system has been shown in diabetic patients and experimental animals, in particular with nephropathy or autonomic neuropathy. The mechanism for this low plasma renin activity (PRA) is poorly understood. In order to clarify this defect, the renin-angiotensin system was studied in alloxan-induced diabetic and age-match control mice. In diabetic animals, kidney renin activity (KRA) was significantly lower than that of the controls, while plasma renin substrate (PRS) concentration was slightly higher and PRA was normal. The amount of injected radiolabeled renin extracted by the kidney was normal, but the amount extracted by the liver was significantly decreased in diabetic animals. On the other hand, the degradation of the extracted renin by both the kidney and the liver was elevated as compared to the controls. This high degradation rate was accompanied by a slight increase in lysosomal protease activity in the kidneys. In in vivo studies, isoproterenol-induced PRA was 20-fold in control animals. In diabetics, isoproterenol-induced PRA was attenuated and rose only four- to fivefold over basal level. The angiotensin converting enzyme (ACE) activity in the kidney was significantly decreased in the diabetic state. It is concluded that there were multiple defects in the renin-angiotensin system in this diabetic model, namely, a depletion of renin storage with subsequent loss of maximal responsiveness to the adrenergic agonist in renin release, an elevation of intrarenal renin degradation together with a deficiency in ACE which would possibly lead to a decrease in intrarenal formation of angiotensin II.
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PMID:Multiple defects in the renin-angiotensin system in alloxan-diabetic kidney. 388 75

Biochemical changes in the placenta were studied using alloxan-induced diabetes mellitus in the female rat. In comparison with a control group (n = 13) the placentas of the diabetic animals (n = 12) had significantly higher glucose, glycogen and protein levels. It was, however, shown that this supply of substrate was inadequately utilised for energy, as ATP/ADP quotient was lower and the ADP content was significantly higher. Metabolism still appeared to take place under aerobic conditions, as evidenced by the unchanged lactate levels. In terms of the protein content of the placentas, the activity of the enzymes we investigated (GOT, GPT, LDH, G-6-PDH, MDH, ICDH) was lowered by 25-44%. These results support the idea of global placental insufficiency in diabetics.
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PMID:Effects of alloxan-induced diabetes mellitus on the metabolism of the rat placenta. 395 50

The long-term effects of different antihypertensive regimens were studied in uninephrectomized beagles with alloxan-induced diabetes mellitus. Mean arterial pressure (MAP) was elevated (P < 0.05) in untreated diabetic dogs. Treatment of diabetic dogs with an angiotensin converting enzyme inhibitor (ACEI; lisinopril), a calcium antagonist (CA;TA-3090), or both lowered MAP. At one year, the RBF, GFR, and SNGFR were similarly elevated (P < 0.05) in all groups of diabetic dogs. The increase in SNGFR present in untreated diabetic dogs was primarily attributable to an increased (P < 0.05) glomerular capillary pressure (PGC). Treatment with lisinopril lowered the PGC to a mean value that was indistinguishable from that for nondiabetic dogs. In contrast, diabetic dogs treated with TA-3090 had an elevated PGC. While untreated diabetic dogs exhibited marked increases in glomerular volume (P < 0.05 vs. nondiabetic dogs), treatment with lisinopril and TA-3090, either alone or in combination, blunted the extent of glomerular hypertrophy observed in diabetic dogs (P < 0.05 vs. untreated diabetic dogs). Proteinuria was similarly reduced (P < 0.05 vs. untreated diabetic dogs) in dogs treated with lisinopril and TA-3090. Combination therapy of diabetic dogs produced a further significant (P < 0.05) decrement in proteinuria. We conclude that although treatment of diabetic dogs with either lisinopril or TA-3090 results in differential effects on PGC; each produces a similar decrement in proteinuria. Further, combination therapy has a greater effect on proteinuria than either agent alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Long-term effects of antihypertensive regimens on renal hemodynamics and proteinuria. 839 Oct 95

In experimental diabetes, diastolic dysfunction of the left ventricle has been associated with collagen-linked glycation. To determine whether less severe hyperglycemia may have similar effects, we gave alloxan to mongrel dogs (group 2) to induce impaired glucose tolerance (IGT) for comparison with normal subjects (group 1). After 6 months, hemodynamic studies were performed in the anesthetized animals. Basal heart rate, aortic pressure, and ejection fraction were comparable in the two groups, but calculated chamber stiffness was increased in group 2, associated with a reduced end diastolic volume and increased pressure. During infusion of dextran, the volume and pressure responses were similarly abnormal in group 2. In the myocardium, the collagen concentration rose with an increased interstitial distribution histologically. To assess glycation, collagen was extracted, digested with collagenase, and measured for fluorescence. Advanced glycation end products were increased in group 2 to 10.6 +/- 1.6 vs. 6.9 +/- 0.7 fluorescent units (FU)/mg collagen in group 1 (P < 0.01). To assess whether this could be pharmacologically prevented, we administered enalapril to inhibit ACE during the 6 months of glucose intolerance to group 3. This resulted in normal glycation and significant reduction in chamber stiffness increment. We gave group 4 animals aminoguanidine daily for 6 months, which prevented abnormal collagen glycation and chamber stiffness. Thus, in animals with IGT, collagen-linked glycosylation appeared to be a major factor affecting diastolic function and was shown to be amenable to pharmacological intervention.
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PMID:Effects of glucose intolerance on myocardial function and collagen-linked glycation. 1038 51

We examined the effects of diabetes on pulmonary capillary endothelial cell (EC) function in diabetic rabbits. One, three and six weeks after alloxan treatment, rabbits were anesthetized and pulmonary endothelium-bound angiotensin converting enzyme (ACE) activity was estimated from the single-pass transpulmonary hydrolysis of benzoyl-Phe-Ala-Pro (BPAP), an ACE specific substrate. ACE activity significantly decreased in 1- and 3-week diabetic rabbits and returned to control levels at 6 weeks. Capillary dilation, parenchymal hemorrhage and erythrocyte clumping were maximal in 3-week diabetic rabbits. We conclude that in the alloxan-diabetic rabbit, there are transient functional and more persistent morphological alterations.
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PMID:Reduced pulmonary endothelium-bound angiotensin converting enzyme activity in diabetic rabbits. 1560 99

Renin-angiotensin system activation is recognized to play an important role in atherosclerosis. This study aimed to verify the antiatherosclerotic effects of ACE inhibition on an experimental model of diabetes and hypercholesterolemia. Diabetes was induced in New Zealand male rabbits with a single dose of alloxan (100 mg/kg, i.v.), and, according to plasma glucose levels obtained after 1 week, the animals were divided into 2 groups (> or =250 mg/dL or <250 mg/dL). Each group was randomly assigned to receive or not quinapril (30 mg/d) added to a 0.5% cholesterol-enriched diet. Animals with high glucose levels at 1 week and that remained high after 12 weeks presented higher triglyceride levels (P < 0.02 versus basal). Those initially hyperglycemic but presenting <250 mg/dL glucose at the end of study formed an additional group. Plasma ACE activity was lower in quinapril-treated animals (P < 0.01 versus untreated groups). However, aorta intima/media ratio and intima area were lower only in the subgroups of quinapril-treated animals with low glucose levels (P < 0.05). Our results support the hypothesis that high plasma glucose may abolish the antiatherosclerotic effect of ACE inhibitors.
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PMID:High glucose levels abolish antiatherosclerotic benefits of ACE inhibition in alloxan-induced diabetes in rabbits. 1577 16

Components of the adrenocortical system (adrenal and blood corticosteroid hormones and hepatic and renal 11beta-hydroxysteroid dehydrogenase activity) and also activity of the most important enzyme of the renin-angiotensin system, tissue and blood angiotensin converting enzyme (ACE) have been investigated in dynamics of alloxan diabetes. The study has shown that the initial period of diabetes is characterized by activation of synthesis and secretion of adrenocortical hormones into blood. High blood glucose and glucocorticoid honnones increase activity of the renin-angiotensin system in lungs and decrease ACE secretion into blood. This is accompanied by a decrease of activity of the renin-angiotensin system in kidneys. Subsequent progression of diabetes resulted in impairments of physiologically determined correlations between the components of these systems. Development of experimental diabetes for 30 days was accompanied by sign of a decrease of the adrenal glucocorticoid function regardless of stable impairments of carbohydrate metabolism. Under these conditions increased adrenal and hepatic 11beta-hydroxysteroid dehydrogenase activity may be responsible for maintenance of elevated levels of the main glucocorticoid in blood and tissues. Factor analysis revealed impairments in intersystem relationships between the adrenocortical and renin-angiotensin systems in experimental diabetes thus suggesting disintegration of regulatory systems.
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PMID:[Adrenocortical and renin-angiotensin systems in dynamics of experimental diabetes]. 2378 45


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