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)

H and K ions play central roles in prorenin processing and secretion, and prorenin is abnormally expressed in H and K disorders. At the surface membrane of juxtaglomerular (JG) cells, K is sensed and regulated by K channels (coupled to Cl channels and activated by excess Ca), Na-K-adenosinetriphosphatase, and a KCl/H exchange transporter (regulated by Ca). In JG cell granular membrane, K flux is regulated by K channels and a KCl/H exchange transporter (activated by Ca). H channels and a H pump reside in the granular membrane, which maintain H concentration in the granular matrix at least two orders of magnitude greater than in cytosol. The H pump may also be responsible for maintaining the acidic matrix required for maximal prorenin processing to renin by prohormone convertase for human renin (PCren), the prorenin convertase. These molecules form the core of a chemiosmotic system, which appears to regulate both prorenin processing and renin secretion. Renin secretion and prorenin processing appear to be of more than causal significance in clinical disorders characterized by chemiosmotic imbalance. A critical review of the literature supports the following general conclusions. First, hyperrenin state defines the initial phase in the pathogenesis of heart disease, diabetes mellitus, and hypertension. Second, low-renin syndrome defines the transition-to-establish phase in the pathogenesis of heart disease, diabetes mellitus, and hypertension in which the key feature is renin secretory hyporesponsivity. Third, renin disorders are usually associated with other endocrine disorders (polyendocrinopathies types I, II, and III), suggesting that renin may be an important molecule in the processing of chemiosmotic forces. The key chemiosmotic molecules (K and H) are also important in the processing and export of most (if not all) hormones. Thus, by regulating K and H homeostasis, renin may regulate the endocrine system.
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PMID:Hydrogen and potassium regulation of (pro)renin processing and secretion. 804 49

Thirty-four patients (65.3+/-3.3 years of age, mean+/-SEM) with hyperkalemia (serum potassium >5.0 mEq/L) had measurement of their renin-aldosterone system. Nineteen patients (56%) had plasma renin activity (PRA) >1.5 ng/mL/h, which was not low, while 15 (44%) had PRA <1.5. Twelve of the 15 hyporeninemic hyperkalemic patients were studied to determine whether their renin-aldosterone system responded to 2 weeks of furosemide, 20 mg daily. Four were nonresponders: PRA averaged 0.3+/-0.1 ng/mL/h, and it did not increase with furosemide or respond to captopril before or after furosemide. Eight patients were responders: PRA averaged 0.6+/-0.2 ng/mL/h and increased with furosemide to 5.5+/-3.4 ng/mL/h. Captopril failed to increase PRA before furosemide, but PRA increased to 15.3+/-8.4 ng/mL/h after furosemide. Plasma aldosterone was low in both nonresponders and responders (3.5+/-1.2 ng/dL vs 5.8+/-2.5 ng/dL) and did not increase significantly with furosemide (4.3+/-1.7 ng/dL vs 8.7+/-2.5 ng/dL). Serum potassium did not fall and therefore did not limit the rise in aldosterone. Renin responders had greater body weight, were predominantly female (6/8 vs 2/4) and were more likely to have diabetes mellitus (7/8 vs 0/4). Plasma atrial natriuretic peptide (ANP) fell with furosemide in 8 of 8 responders and in 1 of the 2 nonresponders in whom it was measured. Neither group had suppressed plasma prorenin levels, indicating no suppression of renin gene expression. These results indicate that many hyperkalemic patients do not have suppressed PRA. Further, a majority of patients with suppressed PRA have high levels of ANP and can respond to diuretic therapy with a rise in PRA and a fall in ANP, suggesting physiologic suppression of the renin system by volume expansion. A minority of hyperkalemic patients with suppressed PRA had PRA that did not increase under these study conditions.
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PMID:Renin-aldosterone system can respond to furosemide in patients with hyperkalemic hyporeninism. 973 29

Involvement of complications is considered to be one of the major factors in the prognosis of diabetes mellitus (DM). Recent studies indicate that most diabetic complications such as nephropathy and hypertension are vascular-originated. Renin-angiotensin involvement, especially changes in ACE activity level, is considered to be a key factor since ACE converts angiotensin I to angiotensin II which is a potent vasoconstrictor and plays a vital role in the regulation of blood pressure. Our present study focused on ACE activity levels along with blood glucose and HbA(1c) levels in diabetic patients with (n=18) or without (n=25) nephropathy as compared to control subjects (n=25). Blood glucose levels were significantly higher in both diabetic groups compared to controls (p<0.001). On the other hand, compared to controls, blood HbA(1c) levels were slightly higher in DM patients without complications whereas they were significantly increased in nephropatic DM patients (p<0.001). There was a very strong increase (p<0.001) at the level of ACE activity in both of the diabetic groups (with nephropathy: 47.11+/-3.70 U l(-1); without complications: 43.72+/-2.93 U l(-1); controls: 25.15+/-2.30 U l(-1)). ACE activity levels were also significantly higher in diabetic patients with nephropathy than in type II DM patients without complication (p<0.01). Our results demonstrate that ACE activity levels are increased in diabetic patients. Additional significant increase in ACE activity levels in diabetic patients with complications such as nephropathy supports the hypothesis that ACE activity has an essential role in the development of complications in diabetes.
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PMID:Angiotensin converting enzyme (ACE) activity levels in insulin-independent diabetes mellitus and effect of ACE levels on diabetic patients with nephropathy. 1068 80

This study compared the cardiovascular and renal effects of long-term telmisartan (3 and 10 mg/kg/day)and lisinopril (10 mg/kg/day) in an animal model combining hypertension and diabetes mellitus. It was a parallel-group study of diabetic, spontaneously hypertensive rats (SHR), treated with control or active treatment for eight months. A non-diabetic SHR control group was run in parallel. Diabetes was induced by streptozotocin (45 mg/kg i.v.) in SHRs aged 9-10 weeks. Animals were treated with telmisartan (3 or 10mg/kg/day), lisinopril (10 mg/kg/day) or vehicle. Plasma glucose levels, blood pressure (BP), and urinary protein and albumin excretion were measured monthly. Telmisartan treatment significantly reduced BP of diabetic SHRs in a dose-dependent manner (p<0.05, low-dose, n= 18; p<0.01, high-dose, n=15). The BP reduction in the lisinopril group was similar to that in the telmisartan 10 mg/kg/day group. Compared with non-diabetic SHRs, untreated diabetic SHRs developed severe proteinuria and albuminuria over the experimental period (p<0.01). In diabetic SHRs, proteinuria and albuminuria were dose-dependently and significantly attenuated by treatment with telmisartan (p<0.01 with the higher dose) and lisinopril (p<0.01). Compared with the untreated diabetic SHRs, cardiac hypertrophy was significantly reduced after treatment with both doses of telmisartan and with lisinopril. Telmisartan, 10 mg/kg/day, but not lisinopril, significantly attenuated the diabetes-induced increase in glomerular volume. In conclusion, telmisartan, 10 mg/kg/day, is at least as beneficial as lisinopril, 10 mg/kg/day, in lowering BP, reducing cardiac hypertrophy and attenuating renal excretion of protein and albumin in this model.
J Renin Angiotensin Aldosterone Syst 2001 Mar
PMID:Comparative antihypertensive and renoprotective effects of telmisartan and lisinopril after long-term treatment in hypertensive diabetic rats. 1188 Oct 63

Arterial wall stiffness is an important independent risk factor for cardiovascular disease in hypertensive patients, which is further exacerbated by co-existent diabetes mellitus. Increased arterial stiffness is directly associated with an increase in pulse wave velocity (PWV) and indirectly with increased central and peripheral blood pressure. Following a two-week placebo run-in period, 27 patients with mild to moderate essential hypertension and Type 2 diabetes mellitus, were randomised to once daily treatment with either telmisartan 40 mg or placebo for three weeks, and after a two-week washout period, crossed-over to the alternative treatment for a further three weeks. Carotid/femoral and carotid/radial PWV were measured non-invasively using the automatic Complior device, and central parameters (central blood pressure, pulse contour analysis, and augmentation index) were measured using the SphygmoCor system, at the start and end of each treatment period. Compared with placebo, treatment with telmisartan significantly reduced carotid/femoral PWV (mean adjusted treatment difference -0.95 m/s, 95% confidence intervals: -1.67, -0.23 m/s, p=0.013), as well as peripheral and central diastolic, systolic and pulse pressure. In conclusion, the results of the this study show that telmisartan is effective in reducing arterial stiffness in hypertensive patients with Type 2 diabetes mellitus, and may potentially have beneficial effects on cardiovascular outcomes, beyond blood-pressure lowering effects in the patient group.
J Renin Angiotensin Aldosterone Syst 2001 Sep
PMID:Effect of telmisartan on arterial distensibility and central blood pressure in patients with mild to moderate hypertension and Type 2 diabetes mellitus. 1188 Nov 2

The Heart Outcomes Prevention Evaluation (HOPE) study was designed to test the hypotheses that two preventive intervention strategies, namely angiotensin-converting enzyme (ACE) inhibition or vitamin E, would improve morbidity and mortality in patients at high risk of cardiovascular events compared with placebo. This review addresses the ACE inhibitor (ACE-I) (ramipril) arm of the study, both on the trial population as a whole, and on the large diabetic subgroup. Patients were included in the study who were considered to be at high risk of future fatal or non-fatal cardiovascular events, by virtue of their age (>55 years), existing or previous cardiovascular disease, or diabetes. Diabetics had at least one other risk factor, either known vascular disease or other factors such as cigarette smoking, high cholesterol or hypertension. Ramipril or placebo was added to concomitant medication, which included, in a substantial proportion of patients, antihypertensive drugs (excluding ACE-I), lipid-lowering agents or aspirin. As a result, despite a history of hypertension in nearly 50% of patients, blood pressure (BP) at baseline was normal and the reduction in BP attributable to ramipril modest (a fall of 3-4 mmHg systolic BP and 1-2 mmHg diastolic). The trial was stopped early on the advice of the Data Monitoring Committee because of convincing evidence of the benefit of ramipril treatment on the combined primary endpoint of cardiovascular death, non-fatal myocardial infarct (MI) and non-fatal stroke (14% vs. 17.8% on ramipril and placebo, respectively; relative risk reduction 22%, p<0.001). This comprised a risk reduction of 32% for stroke, 20% for MI, 26% for cardiovascular death and 16% for all-cause mortality, as well as a reduction in the risk of several other endpoints including heart failure and revascularisation procedures. The results among the 3577 diabetic subjects were even more striking, with a reduction of 25% in the combined primary endpoint. This reduction in the combined endpoint and in particular the reduction in MI far exceeded that which would be expected from the modest fall in BP. Furthermore, a multiple regression analysis of the diabetic subgroup showed similar relative risk reductions even after allowing for the effects of the fall in BP. Possible explanations for the non BP-mediated benefits of ramipril include reduction of angiotensin II-induced intimal and vascular smooth muscle proliferation and possible plaque stabilisation. The HOPE study results show that it is both safe and beneficial to lower BP that is already within the 'normal' range, particularly in patients with known vascular risk factors. This should greatly extend the use of ACE-I to a wider group of patients - not only those with left ventricular dysfunction, hypertension or diabetic microalbuminuria, but to the sort of high-risk patients who are currently given prophylactic treatment with aspirin.
J Renin Angiotensin Aldosterone Syst 2000 Mar
PMID:The HOPE Study (Heart Outcomes Prevention Evaluation). 1196 89

The RENAAL Study is a double-blind, placebo-controlled trial to evaluate the renal protective effects of losartan in Type 2 diabetic patients with nephropathy. The study has enrolled 1513 patients and is expected to continue for 3.5 years after the last patient has been entered. Eligible patients must have a urinary albumin:creatinine ratio of at least 300 mg/g and serum creatinine between 1.3 to 3.0 mg/dL. Eligible hypertensive or normotensive patients are randomised to receive either losartan or placebo, in addition to their existing antihypertensive therapy. Medications that block angiotensin production or action, are excluded. The primary endpoint is a composite of the time to first event of doubling of serum creatinine, end-stage renal disease, or death; secondary endpoints include cardiovascular events, progression of renal disease, and changes in proteinuria; tertiary endpoints include quality of life, healthcare resource utilisation, and amputations. Patients include Caucasians (48.6%), Blacks (15.2%), Asians (16.7%), and Hispanics (18.2%). Baseline urinary albumin:creatinine ratio and serum creatinine levels average 1867 mg/g and 1.9 mg/dL, respectively. Mean systolic and diastolic blood pressures are 153 and 82 mmHg, respectively. RENAAL will document whether blockade of the AII receptor with losartan produces clinical benefits in patients with Type 2 diabetes and nephropathy.
J Renin Angiotensin Aldosterone Syst 2000 Dec
PMID:The losartan renal protection study--rationale, study design and baseline characteristics of RENAAL (Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan). 1196 19

Poor glycaemic control and high blood pressure are two important risk factors for the development of retinopathy and nephropathy in Type 1 diabetes. The renin-angiotensin-aldosterone system (RAAS) may be involved in this process, since treatment with angiotensin-converting enzyme (ACE) inhibitors postpones the development of these complications. We investigated whether plasma renin activity (PRA), plasma angiotensin II (Ang II) and atrial natriuretic peptide (ANP) differed in Type 1 diabetic patients compared with healthy controls. We recruited 80 patients with Type 1 diabetes of more than 10 years' duration and 75 age-matched controls. We found that PRA and Ang II concentrations were significantly lower in patients than in the controls. The levels of ANP, on the other hand, were higher in patients than in controls. PRA correlated negatively to the mean value of HbA(1c) during the previous five years. PRA and Ang II were significantly lower in patients with mean HbA(1c) >8.4% compared with those with mean HbA(1c) <7.2%. In summary, we found patients with Type 1 diabetes to have RAAS suppression and increased ANP levels, suggesting a state of fluid retention.
J Renin Angiotensin Aldosterone Syst 2000 Dec
PMID:The renin-angiotensin-aldosterone system is suppressed in adults with Type 1 diabetes. 1196 22

Effective reduction in blood pressure (BP) improves survival and morbidity in hypertensive patients. Combination therapy with multiple antihypertensive agents is frequently required in clinical practice and therapeutic trials to achieve target BP. Patients at elevated cardiovascular risk achieve the greatest benefit from equivalent reduction in BP and also require more stringent BP control. In patients with hypertension and diabetes mellitus or renal disease, BP control is of primary importance and blockade of the renin-angiotensin system (RAS) should be the initial therapeutic intervention. Choice of combination therapy has been insufficiently studied in major clinical cardiovascular endpoint trials. Diuretic therapy remains the logical addition to RAS blockade. Despite previous debate, the available evidence suggests long-acting calcium-channel blockers are also a safe and very effective addition to improve BP control further. The choice of antihypertensive combination therapy should not override the fundamental necessity of lowering BP to target levels.
J Renin Angiotensin Aldosterone Syst 2002 Jun
PMID:Calcium channel blockade in combination with angiotensin-converting enzyme inhibition or angiotensin II (AT(1)-receptor) antagonism in hypertensive diabetics and patients with renal disease and hypertension. 1222 47

Interest in the renin-angiotensin-aldosterone system (RAAS) has increased since the development of angiotensin-converting enzyme (ACE) inhibitors. It has been discovered that the potential uses of this class of treatment extend far beyond their initial developmental role as antihypertensives, and they are now used routinely in the treatment of heart failure, nephropathy, myocardial infarction and diabetes. However, there is more to RAAS blockade than just inhibition of angiotensin II, and inhibition of aldosterone is becoming recognised as an additional therapeutic manoeuvre in chronic heart failure. Since inhibition of the RAAS at the level of ACE is now seen to be an important therapy in diabetes; the purpose of this article is to explore the potential benefits of additional aldosterone inhibition in Type 2 diabetes mellitus.
J Renin Angiotensin Aldosterone Syst 2002 Sep
PMID:The potential benefits of aldosterone antagonism in Type 2 diabetes mellitus. 1256 64


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