Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiotensin I Converting Enzyme (ACE), which is synthesized by vascular endothelial cells, can be elevated in some diabetic subjects. To study if serum ACE can be elevated in subjects with high risk for malignant microangiopathy, 34 normotensive type I, insulin-dependent diabetic subjects with persistent microalbuminuria (30-300 mg/24 h) were compared for serum ACE activity (Liebermann's method) with 30 normotensive, normoalbuminuric type I, insulin-dependent diabetic subjects of same age (33 +/- 15 (M +/- SD) vs 39 +/- 14 years), sex (13 F/21 M vs 15 F/15 M), stage of retinopathy (14 vs 16 nil/11 vs 7 background/6 vs 4 preproliferative/3 vs 3 proliferative), HbA1c (7.7 +/- .9 vs 8.2 +/- 1.0%). Serum ACE activity of diabetic subjects were also compared with 120 age and sex related healthy controls. Serum ACE activity was higher in type I, insulin-dependent diabetic subjects with microalbuminuria than in those with normoalbuminuria (406 +/- 114 vs 359 +/- 97 IU/l; p = 0.05), or in controls (307 +/- 95 IU/l; p = 0.0001). Normoalbuminuric subjects also had higher ACE activity than controls (p = 0.02). In diabetic subjects, serum ACE activity was not related to diabetes duration (r = 0.1; ns), stage of retinopathy (r = 0.06; ns), HbA1c (r = 0.02; ns), or to blood pressure (r = 0.03; ns), but was related to urinary albumin excretion (r = 0.28; p = 0.03) in diabetic subjects. However, stage of retinopathy was related to diabetes duration (r = 0.74; p = 0.0004) and to age (r = 0.42; p = 0.003) in these subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Increase of activity of angiotensin-converting enzyme in insulin-dependent diabetic patients with permanent microalbuminuria]. 133 56

To investigate plasma renin and prorenin levels in non-insulin-dependent diabetes mellitus (NIDDM) and their relation with autonomic nervous function and renal impairment, we measured plasma renin and prorenin levels in 39 NIDDM patients. The patients included 21 males and 18 females, aged 56.3 +/- 6.2. Thirty-four normal age-matched subjects served as controls. Autonomic nervous function was evaluated in 23 patients by the performance of cardiovascular reflex tests. The plasma renin concentration was measured by angiotensin I generation after the addition of an exogenous substrate. Plasma prorenin was activated by trypsin. The results showed that the plasma renin concentration was similar between NIDDM patients and normal subjects, while plasma prorenin was higher in NIDDM patients. No correlation existed between the plasma renin or prorenin levels and autonomic nervous function. The patients with abnormally high levels of prorenin also had a similarly high plasma renin level but not a high creatinine clearance (Ccr) or daily proteinuria. The plasma renin level was correlated inversely with daily proteinuria but not with Ccr. These results suggest that the high plasma prorenin levels in some diabetic patients cannot be explained by renal impairment, poor prorenin conversion or autonomic dysfunction. The hyporeninemia in some patients may be related to microvascular involvement of the kidney.
 ...
PMID:Plasma prorenin and renin levels in non-insulin-dependent diabetes mellitus. 136 16

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.
 ...
PMID:Molecular genetic approaches to the identification of genes involved in the development of nephropathy in insulin-dependent diabetes mellitus. 145 65

We previously showed that renal prokallikrein synthesis is reduced in streptozotocin (STZ)-diabetic rats. Plasma renin activity is also reduced in diabetic rats. To investigate the molecular mechanisms underlying these changes, we examined the effects of diabetes and insulin treatment on renal kallikrein and renal renin mRNA levels and the activities of these enzymes. Rats made diabetic by STZ were either treated with 1.5 to 1.75 U PZI insulin daily to maintain moderate hyperglycemia (plasma glucose 200 to 300 mg/dl, D + I) or left untreated to produce severe hyperglycemia (plasma glucose greater than 400 mg/dl, D). Control (C) rats were also studied. After three weeks, renal kallikrein mRNA was reduced 50% in D rats. A proportional reduction in immunoreactive kallikrein was also observed (37.8 +/- 2.5 vs. 55.8 +/- 6.8 ng/mg protein, D vs. C, P less than 0.001). Kallikrein mRNA and immunoreactive kallikrein levels in D + I rats were not different from C rats. Renin mRNA level was also markedly reduced in D rats, compared to C rats. This was associated with reduced plasma renin concentration (4.5 +/- 0.2 vs. 10.5 +/- 1.6 ng Ang I/ml/hr, D vs. C, P less than 0.01). However, renal renin concentration was unchanged (0.84 +/- 0.17 vs. 0.84 +/- 1.3 micrograms Ang I/mg protein/hr, D vs. C). In D + I rats, renin mRNA level and plasma renin concentration were not different from C levels. However, renal renin concentration was increased (1.49 +/- 0.27 micrograms Ang I/mg protein/hr) compared to C rats (P less than 0.05). beta-actin mRNA levels were unchanged in either diabetic rat group.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effects of diabetes and insulin on expression of kallikrein and renin genes in the kidney. 151 1

A universal underlying abnormality in the pathogenesis of hypertension, atherosclerosis, myocardial dysfunction, and diabetic glomerulosclerosis involves alteration in smooth muscle cell structure, function, and growth. Angiotensin II, through its effects on contractility, growth, and the sympathetic nervous system, may potentially play a key role in this pathologic process and, thus, contribute to the development of these cardiovascular and renal complications of diabetes mellitus. Angiotensin-converting enzyme inhibitors and some direct renin inhibitors prevent or slow the progression of some of these complications, which further suggests a pathologic role for the reninangiotensin system in diabetes mellitus.
 ...
PMID:Effect of the renin-angiotensin system in the vascular disease of type II diabetes mellitus. 158 Feb 75

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.
 ...
PMID:Plasma renin activity and plasma prorenin assays. 191 95

The pathogenesis of diabetic nephropathy remains elusive. A role for renal prostaglandins in antagonizing the hormonal effects of renin-angiotensin II has been postulated as a putative factor leading to hyperfiltration in patients with Type 1 (insulin-dependent) diabetes mellitus. Our aim was to elucidate the effects of angiotensin II on kidney haemodynamics and on blood pressure in eight normal subjects, in nine normotensive, in nine hypertensive with normal sodium-lithium countertransport activity in erythrocytes, in seven hypertensive without and in eight hypertensive Type 1 diabetic patients with microalbuminuria and with high sodium-lithium countertransport activity in erythrocytes. Angiotensin II infusion (4 ng.kg-1.min-1 for 60 min) decreased the glomerular filtration rate to a greater extent in normal subjects (-20%), than in normotensive patients (-5% p less than 0.01), in hypertensive patients with normal sodium-lithium countertransport activity in erythrocytes (-8% p less than 0.01) in hypertensive patients with high sodium-lithium countertransport (-6% p less than 0.01) and in hypertensive microalbuminuric patients (-5% p less than 0.01) with Type 1 diabetes. The urinary excretion rate of vasodilatory prostaglandins was two-three fold higher in all patients than in normal subjects. Acute indomethacin treatment restored a normal response to angiotensin II infusion in normotensive patients, but did not change the renal haemodynamic response in normal subjects. With regard to hypertensive patients with and without microalbuminuria indomethacin treatment restored a normal response to angiotensin II in some but not all patients.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Impaired response to angiotensin II in type 1 (insulin-dependent) diabetes mellitus. Role of prostaglandins and sodium-lithium countertransport activity. 193 64

Angiotensin carboxypeptidase (ACP) activity has been detected in urine samples from normal subjects and patients with hypertension and diabetes by determining the enzyme's ability to convert angiotensin I to des-Leu angiotensin I. Gel filtration chromatography of a concentrated urine sample indicated that about equal amounts of the enzyme exist as 100 kDa and 500 kDa molecular weight forms, respectively. This ACP activity co-eluted with activity that cleaved histidine from des-Leu angiotensin I to form angiotensin II and activity that cleaved tyrosine from benzyloxycarbonyl-glutamyl-tyrosine (ZGT). These results suggest that the urinary ACP activity is due to cathepsin A as we have reported previously for the porcine kidney enzyme. Analysis of sequential urine samples from a single individual over a 6-day period revealed as much as a 6-fold fluctuation in creatinine-normalized ACP activity. Of five male healthy adult subjects, the creatinine-normalized urinary ACP activity ranged from 1.7 to 3.7 mU/mL with a mean of 2.8 mU/mL. However, five male patients with renovascular hypertension had elevated levels of ACP activity with a mean of 11.6 mU/mL. Of five male patients with diabetic nephropathy, all had elevated ACP activity levels with a mean of 21.0 mU/mL. It is concluded that ACP activity in the urine is due to cathepsin A probably derived from kidney tissue, and that the release is increased in patients with kidney damage. We suggest that urinary ACP activity should be evaluated further for a possible relationship to renal hypertension and as a potentially early marker for diabetic nephropathy.
 ...
PMID:Angiotensin carboxypeptidase activity in urine from normal subjects and patients with kidney damage. 201 86

Elevation of glomerular filtration rate (GFR) is a feature of diabetes mellitus in humans and in animal models. Angiotensin II has been implicated as a mediator of GFR in diabetes. The acute effect of inhibition of angiotensin converting enzyme with captopril on renal haemodynamic and endocrine parameters was therefore studied in 14 normotensive male Type 1 diabetic patients, and the responses compared with those in five normal male control subjects. Following captopril 12.5 mg orally the diabetic patients exhibited an acute fall in GFR from 122 +/- 3.8 to 113 +/- 4.5 ml min-1 1.73-m-2 (p less than 0.02) and a rise in renal plasma flow (RPF) from 670 +/- 57 to 797 +/- 46 ml min-1 1.73-m-2 (p less than 0.01) which resulted in a fall in filtration. This did not occur in normal control subjects. Natriuresis occurred only in normal control subjects. There was no change in urinary excretion of PGE2 or kallikrein in either group but excretion of 6-keto-PGF1 alpha fell in the diabetic patients. There was a significant correlation between glycosylated haemoglobin and baseline RPF (rs = -0.79, p less than 0.001) and filtration fraction (rs = 0.83, p less than 0.001) that persisted when the change in these variables following captopril was analysed. Our results are compatible with the response to ACE inhibition in diabetic patients being secondary to inhibition of angiotensin II and suggest that this response may be related to blood glucose control.
 ...
PMID:Blood glucose control determines the renal haemodynamic response to angiotensin converting enzyme inhibition in type 1 diabetes. 213 98

Diabetes-associated hypertension is accompanied by high levels of body sodium and cardiovascular hyper-reactivity to noradrenaline. Captopril, a promising drug for the treatment of hypertension in diabetics, may influence sodium metabolism and adrenergic pathways. This possibility was investigated in 11 patients with non-azotaemic diabetes mellitus and hypertension, studied after a 3-week placebo phase and after an 8-week phase of captopril treatment (50-100 mg/day). Blood pressure, exchangeable body sodium, blood volume, plasma renin activity, angiotensin II (Ang II), aldosterone, catecholamine levels and the pressor reactivity to infused Ang II or noradrenaline were measured. Compared with placebo, captopril caused a significant decrease in arterial pressure and stimulation of plasma renin activity. Exchangeable sodium, blood volume, plasma Ang II, aldosterone, noradrenaline and adrenaline levels, the pressor and aldosterone responsiveness to infused Ang II and the pressor response to infused noradrenaline (alone or combined with atropine) were not modified. These findings suggest that in hypertensive diabetics angiotensin converting enzyme inhibition causes a marked decrease in blood pressure. The mechanism of action is unrelated to changes in body sodium or noradrenergic-dependent pressor reactivity. In the stable phase of therapy, Ang II-dependent pathways are left unaltered when captopril is administered twice a day.
 ...
PMID:Cardiovascular regulation during angiotensin converting enzyme inhibition with captopril in diabetes-associated hypertension. 216 58


1 2 3 4 5 6 7 8 9 10 Next >>