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)

This study was initiated to explore the possibility that an increase in the supply of gluconeogenic precursors contributes to the overproduction of glucose by the liver in NIDDM patients. To address this issue, a form of experimental NIDDM was produced in rats by injecting a low dose (38 mg/kg) of STZ and comparing lactate and alanine production and PDH activity in skeletal muscle and isolated adipocytes from normal and diabetic rats. Skeletal muscle lactate production was measured by using a hindlimb perfusion technique and was significantly greater (P < 0.01) in the diabetic rats compared with two groups of control rats: one perfused at normal glucose levels and the other perfused at glucose concentrations comparable with those observed in diabetic rats. Alanine production by hindlimb from diabetic rats was 46% greater than hindlimbs from control rats perfused at normal glucose levels (P < 0.01) but was not significantly greater than control rats perfused at diabetic glucose levels. The percentage of glucose converted to lactate by muscle from both control groups was 4-5%, significantly lower than the 18% conversion rate observed in diabetic animals (P < 0.001). An increase in the ratio of lactate produced/glucose transport by isolated adipocytes from diabetic rats also was observed when measured in both the basal state (0.65 +/- 0.12 vs. 0.15 +/- 0.03, P < 0.01) and in the presence of maximal amounts of insulin (0.15 +/- 0.02 vs. 0.04 +/- 0.01, P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lactate production and pyruvate dehydrogenase activity in fat and skeletal muscle from diabetic rats. 144 95

1. Streptozotocin diabetic rats were treated with captopril (50 mg l), an angiotensin converting enzyme-inhibitor, in drinking water for 20 weeks. 2. Systolic blood pressure and 24-hr urinary excretions of heparan sulfate and albumin were done at 2, 8, 16 and 20 weeks. 3. At the end of 20 weeks, all rats were killed, kidneys removed and glomeruli isolated. 4. Total glycosaminoglycan and heparan sulfate synthesis were determined by incubating glomeruli in the presence of 35S-sulfate. 5. Captopril significantly lowered blood pressure in diabetic rats 8 weeks after treatment. 6. Diabetic glomeruli synthesized less total glycosaminoglycan and heparan sulfate than glomeruli from nondiabetic rats. 7. Further characterization of heparan sulfate by ion-exchange chromatography showed that the fraction eluted with 1 M NaCl was significantly lower and the fraction eluted with 1.25 M NaCl significantly higher in diabetic than in normal rats. 8. Therapy with captopril normalized not only glomerular synthesis and content but also various fractions of heparan sulfate in diabetic rats. 9. Excretions of heparan sulfate and albumin were significantly higher in diabetic than in nondiabetic rats. 10. Captopril therapy did significantly lower but not normalize both these excretions in diabetic rats. 11. The data suggest that catopril therapy improves albuminuria through preservation of glomerular heparan sulfate and prevention of its urinary loss in diabetic rats.
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PMID:Prevention of albuminuria by captopril in diabetic rats. 205 28

1. Streptozotocin diabetes was induced in Wistar-Kyoto rats fed a 50% protein diet. Animals were randomized to receive either the ACE inhibitor ramipril, 1 mg/L in drinking water (n = 7), or no treatment (n = 7) and were studied for 6 months. Blood glucose, body weight and glomerular filtration rate (GFR) were measured at 0, 1, 4, 8 and 16 weeks of diabetes and urinary albumin excretion was measured every 8 weeks. 2. In both groups, GFR increased significantly within 1 week of induction of diabetes (P less than 0.001) and thereafter remained stable. There was no difference in GFR between the treated and untreated groups. 3. Urinary albumin excretion increased progressively in both groups throughout the study. Ramipril treatment reduced albuminuria by approximately 50% at weeks 16 and 24 (P less than 0.01). 4. The amelioration of diabetic albuminuria by ACE inhibition, in the setting of high dietary protein intake, may have important implications for the treatment of human diabetic nephropathy.
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PMID:Ramipril reduces albuminuria in diabetic rats fed a high protein diet. 252 67

This study has evaluated the effects of the angiotensin converting enzyme inhibitor Enalapril on glomerular ultrastructure and albuminuria in normotensive and hypertensive diabetic rats. Streptozotocin-diabetes was induced in Wistar Kyoto and spontaneously hypertensive rats. Enalapril was administered in drinking water in diabetic normotensive, control hypertensive and diabetic hypertensive rats. Enalapril therapy prevented an increase in glomerular basement membrane thickness in diabetic normotensive, control hypertensive and diabetic hypertensive rats without any significant effect on fractional mesangial volume. Enalapril decreased albuminuria in diabetic normotensive, control hypertensive and diabetic hypertensive rats. Thus, enalapril retards the development of glomerular basement membrane thickening and albuminuria in the rat, in the presence or absence of hypertension.
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PMID:Enalapril retards glomerular basement membrane thickening and albuminuria in the diabetic rat. 255 9

The aim of this study was to compare the renal effects of angiotensin converting enzyme (ACE) inhibition with calcium channel blockade in a model combining genetic hypertension with diabetes. Streptozotocin diabetes was induced in spontaneously hypertensive rats (SHR). The animals were then randomized to receive no treatment, the ACE inhibitor, perindopril, or the dihydropyridine calcium antagonist lacidipine. Body weight, systolic blood pressure, glycemic control, renal function, and albumin excretion rate (AER) were assessed serially over the 32-week study period. At week 32 the animals were killed and glomerular volume was measured. Both antihypertensive regimens significantly reduced systolic blood pressure in diabetic SHR. There was no significant difference in glycemic control, serum creatinine, or glomerular filtration rate among the three groups at week 32. The ACE inhibitor perindopril significantly reduced AER and glomerular hypertrophy over the 32 weeks, whereas the calcium antagonist lacidipine failed to reduce AER or glomerular hypertrophy. Thus, in contrast to the effects of ACE inhibition, calcium channel blockade with lacidipine, despite significantly reducing blood pressure, failed to reduce renal injury in this model. These results support the hypothesis that antihypertensive regimens may differ in their capacity to protect the diabetic kidney, despite similar effects on systemic blood pressure.
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PMID:Comparison of effects of ACE inhibition with calcium channel blockade on renal disease in a model combining genetic hypertension and diabetes. 773 98

We examined the influence of the new angiotensin-converting enzyme inhibitor (ACEI) fosinopril on function and perfusion of the diabetic rat heart. Streptozotocin-diabetic rats (60 mg/kg body weight) were treated with fosinopril (10 mg/kg body weight/day) for 4 months. Cardiac performance was analyzed in the isolated heart perfused at constant volume. Epicardial perfusion was determined by measuring epicardial fluorescence changes after injection of FITC-dextrane (3 kDa) as described previously. As compared with controls, fosinopril prevented or diminished the increase in end-diastolic pressure (EDP), coronary perfusion pressure (CPP), and vascular resistance in diabetes. The intravascular volume strongly reduced in diabetes was increased, and the epicardial perfusion rate was accelerated in hearts of diabetic rats treated with fosinopril. The vascular exchange diminished in hearts of untreated diabetic rats was enhanced, and the transcapillary permeability was slightly accelerated at low flow rates. These data indicate that treatment of streptozotocin-diabetic rats with fosinopril prevents severe disturbances of coronary autoregulation and at least partly the impairment of cardiac perfusion generally observed in diabetic rats. Together with previously published morphological data demonstrating an inhibition of interstitial and perivascular fibrosis in hearts of diabetic rats with fosinopril, our observations suggest that ACE inhibition by fosinopril is cardioprotective in diabetes.
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PMID:Influence of angiotensin-converting enzyme inhibition by fosinopril on myocardial perfusion in streptozotocin-diabetic rats. 865 60

It is generally accepted that hypertension and other vascular pathologies increase in diabetes mellitus (DM) patients as a result of the renin-angiotensin-aldosterone (RAA) system. In this study, changes in the renin-angiotensin-aldosterone (RAA) system level was determined in Streptozotocin (STZ)-injected rats. A total of 46 female Wistar albino rats (180-220 g body weight) was utilized in these experiments. STZ was given intraperitoneally to induce diabetes in rats. Streptozotocin (60 mg kg(-1) body weight) was dissolved in 0.1 m citrate--phosphate buffer (pH 4-5). The non-diabetic rats were injected with sterilized buffer alone to act as a control group. Blood glucose levels were 398+/-8.2 mg dl(-1), 488+/-11.75 mg dl(-1) and 658+/-29.6 mg dl(-1) at days 3, 12 and 30 respectively. The level of plasma renin activity (PRA) was measured as 7.69+/-1.07 ng ml(-1) h(-1); 1.82+/-0.22 ng ml(-1) h(-1) and 0. 67+/-0.12 ng ml(-1) h(-1) at days 3, 12 and 30, respectively. These values showed that the PRA levels are decreased with increased time period. Serum angiotensin converting enzyme (ACE, E.C. 3.4.15.1) levels were increased at days 12 and 30 (p<0.05 and p<0.005), whereas serum aldosterone levels were increased at days 3 and 12 (p<0.05). The level of urea and creatinine increased at days 12 and 30 (p<0.05 and p<0.005, respectively) when compared to the control group. The data from these experiments indicate that the PRA level decreased whereas ACE activity level increased in diabetic rats compared with the control. Aldosterone levels increased at the first stage of the experiment, but then decreased by the end of the experiment as a result of changes in renin and ACE levels.
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PMID:The study of renin-angiotensin-aldosterone in experimental diabetes mellitus. 1122 74

In this study, the vascular responses of diabetic rat femoral arteries to epinephrine were investigated. The effects of lisinopril (ACE inhibitor) on vascular epinephrine sensitivity were also tested in a different group. This study was carried out in sodium pentobarbital-anesthetized rats 8 weeks after induction of diabetes with streptozotocin. After extensive dissection of the femoral arteries with adventitial stripping, epinephrine and chlorpromazine were applied to the vascular wall, and their vascular effects were compared in streptozotocin-diabetic (STZ-D), lisinopril-administered streptozotocin-diabetic (LASTZ-D), lisinopril-administered nondiabetic (LAND), and non-diabetic (ND) groups. Vasoconstriction was induced by epinephrine in all groups in a dose-response fashion. There were statistically significant differences in maximum percent constriction between STZ-D and LASTZ-D groups. There was also a significant increase in sensitivity to epinephrine in the STZ-D group. The vasoconstriction induced by epinephrine was relieved by chlorpromazine in all groups. Results suggest that there are important functional abnormalities in the responses of vessels to epinephrine in diabetics, and that the attenuation of vasoconstriction by ACE inhibitors may have beneficial effects in microsurgical procedures performed on diabetic patients. Topically-applied chlorpromazine appears to be effective in relieving vasospasm due to epinephrine, and may be a useful tool to resolve perioperative vascular spasm in microsurgical procedures for diabetic and non-diabetic patients.
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PMID:Vascular effects of epinephrine, lisinopril, and chlorpromazine in diabetic and non-diabetic rats. 1048 May 64

Clinical studies indicate a nephro-protective effect in conjunction with the use of ACE inhibitors. This study's aim was to determine whether ACE inhibitors influence the metabolism of glomerular cells in addition to their known hemodynamic effects. Streptozotocin diabetic rats were treated with lisinopril (DLis 1.5 mg/l water), or hydralazine (Dhyd, 50 mg/l water) over 4 weeks. Untreated diabetic rats (DC) and non-diabetic rats (C) served as controls. After four weeks of treatment, urinary excretion of albumin, blood pressure and metabolic control (Glyc-Hb) were measured. After treatment glomeruli were isolated and homogenized, and beta-NAG and total proteolytic activity against azocasein were measured. Glycated hemoglobin levels were similar in all diabetic groups (DC, 12%, Dhyd, 10%; DLis 11%). Blood pressure of DLis rats (79 +/- 3 mmHg) and DHyd rats (46 +/- 2 mmHg) was lower than that of DC rats (111 +/- 3 mmHg). Urinary albumin excretion of diabetic groups was lowest in DLis. Diabetic rats showed a decrease in glomerular beta-NAG (10 vs. 60.5 U/g protein) and total proteolytic activity against azocasein (148 vs. 170 U/mg protein hour) compared to non-diabetic rats. Lisinopril increased beta-NAG (30 vs. 14 U/g protein) and total proteolytic activity (160.5 vs. 141.5 U/mg protein hour) compared with hydralazine. Our study confirms that the nephro-protective effect of ACE inhibitors is partially due to modulatory effects on the metabolism of basement membrane proteins.
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PMID:The influence of the ACE inhibitor lisinopril on the glomerular metabolism of proteolytic enzymes in diabetic rats. 1145 May 1

To evaluate the effects of angiotensin converting enzyme inhibitor (ACE-I) on diabetic cardiovascular complications, a streptozotozin (STZ, i.p., 70 mg/kg BW) induced diabetes rat model was used. The animals were separated into four major groups including: control (NSS), STZ-treated rats, STZ-treated rats received daily oral feeding of cilazapril starting one day after STZ injection (STZ-C1), and STZ-treated rats received daily oral feeding of cilazapril eight weeks after the STZ injection (STZ-C8). Within the groups of STZ-C1 and STZ-C8, the animals were also divided into three subgroups of six rats that received different doses of cilazapril treatment, 0.01 mg/Kg BW, 1 mg/Kg BW, and 10 mg/Kg BW. By using the modified isolated heart model, the parameters of mean arterial pressure (MAP), heart rate (HR), left ventricular isotonic contraction (LVIC), aortic flow rate (AFR), coronary flow rate (CFR), and ratio of heart weight per body weight (R) were assessed for each groups 8 and 20 weeks after the STZ injections. Moreover, the changes of wall thickness of the left ventricular wall (LV), right ventricular wall (RV), and interventricular septal wall (IVS) were monitored from the scanning electron micrographs of each heart. The results indicated that in both STZ-C1 and STZ-C8, the diabetic hypertension could be prevented or treated by anti-hypertensive doses of cilazaprils. Besides, the values of AFR, CFR, and LVIC were significantly increased when comparing between the STZ and STZ-C1 or STZ-C8. The results of morphological examinations indicated that: (1) left ventricular walls of the three hearts of STZ-rats had increased significantly more than controls. (2) Right ventricular walls and interventricular septal walls were not significantly different among STZ-rats, cilazapril treated STZ-rats and age matched controls. Therefore, it is concluded that ACE-I could act either as a cardioprotective or therapeutic agent for diabetic hearts. Both major anti-hypertension and anti-trophic effects of ACE-I have already been elucidated.
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PMID:Effects of ACE-I on diabetic cardiovascular complications: anti-hypertensive and non-antihypertensive doses. 1152 49


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