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)

Insulin therapy, administered by continuous subcutaneous infusion with osmotic pumps over a 28 day period at doses of 2.5 and 5.0 units/day, resulted in a statistically significant increase in body weight of diabetic rats. The concentration of blood glucose was reduced by 68% to 109 mg/dl blood sugar by the higher dose of insulin and only partial control of diabetes was achieved by the lower dose (185 mg/dl blood sugar, -39%). Blood pressure was normalized by both doses of insulin. Elevated serum angiotensin converting enzyme activity and plasma renin activity, expressed as generated angiotensin I, were unaffected by the lower dose of insulin, but were reduced by 26% and 40%, respectively at the higher dose. These data suggest that elevated serum ACE and plasma renin activity, commonly found in the streptozotocin-diabetic rat, may not be primarily responsible for hypertension in this model.
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PMID:Effect of insulin pump therapy on blood pressure and the renin-angiotensin system of diabetic rats. 218 97

Adenylate cyclase in liver plasma membranes from streptozotocin-diabetic (STZ) or BB/Wor spontaneously diabetic rats showed increased responsiveness to GTP, glucagon, fluoroaluminate, and cholera toxin. Basal or forskolin-stimulated activity was unchanged in STZ rats, but increased in BB/Wor rats. No change in the alpha-subunit of Gi (alpha i) was observed in STZ or BB/Wor rats using pertussis toxin-stimulated [32P]ADP-ribosylation. Immunodetection using antibodies against the COOH-terminal decapeptides of alpha T and alpha i-3 showed no change in alpha i in STZ rats and a slight decrease in BB/Wor rats. Angiotensin II inhibition of hepatic adenylate cyclase was not altered in either diabetic rat. In both models of diabetes, Gs alpha-subunits were increased as measured by cholera toxin-stimulated [32P]-ADP-ribosylation of 43-47.5-kD peptides, reconstitution with membranes from S49 cyc- cells or immunoreactivity using antibodies against the COOH-terminal decapeptide of alpha s. These data indicate that STZ-diabetes increases hepatic Gs but does not change Gi or adenylate cyclase catalytic activity. In contrast, BB/Wor rats show increased hepatic Gs and adenylate cyclase. These changes could explain the increase in hepatic cAMP and related dysfunctions observed in diabetes.
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PMID:Guanine nucleotide binding regulatory proteins and adenylate cyclase in livers of streptozotocin- and BB/Wor-diabetic rats. Immunodetection of Gs and Gi with antisera prepared against synthetic peptides. 249 95

1. To investigate atrial natriuretic factor (ANF) and its relationship to the renin system in diabetes, we measured plasma immunoreactive ANF and plasma renin activity (PRA) in 27 non-ketotic diabetic patients without evidence of cardiac or overt renal disease, and compared them with 26 age- and sex-matched normal subjects. 2. Diabetic patients were divided prospectively into poor (PGC, n = 14) or moderate (MGC, n = 13) glycaemic control depending on their concurrent plasma glycohaemoglobin (HbA1) levels (greater than 9% or less than 9%, respectively). Plasma ANF was elevated in PGC diabetic patients (15.7 +/- 1.8 fmol/ml, mean +/- SEM) compared with MGC diabetics (9.9 +/- 0.8 fmol/ml, P less than 0.001) and normal subjects (10.1 +/- 1.3 fmol/ml, P less than 0.05). 3. In contrast, PRA was lower in the PGC diabetic patients (1.3 +/- 0.3 pmol of angiotensin 1 h-1 ml-1) compared with the other groups (2.5 +/- 0.5 and 2.1 +/- 0.2 pmol of angiotensin I h-1 ml-1, P less than 0.05). Diabetic groups had proportionally more patients with high prorenin values (over 30 ng h-1 ml-1) than the normal group, but there was no difference between the diabetic groups. 4. Among the diabetic patients, ANF was directly related to HbA1 (r = 0.49, P less than 0.005) and urinary albumin excretion (r = 0.40, P less than 0.02), and was inversely related to PRA (r = 0.36, P less than 0.04) and plasma creatinine (r = -0.42, P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increased plasma atrial natriuretic factor and reduced plasma renin in patients with poorly controlled diabetes mellitus. 252 63

We examined ten patients with type I diabetes mellitus and ten age- and sex-matched healthy controls. Median duration of diabetes was 7 years (range 0.5-24). None of the diabetic patients had hypertension, microalbuminuria, or proliferative retinopathy. Maximal specific binding capacity for angiotensin II to thrombocytes was significantly increased in diabetics (Bmax 11.9 +/- 1.6 sites per cell vs 7.0 +/- 0.9 in controls; P less than 0.01). In contrast, maximal binding for atrial natriuretic factor tended to be lower in type I diabetics (8.84 +/- 1.25 sites per cell vs 16.8 +/- 2.97; P less than 0.07). There was no difference of apparent dissociation constant (KD) for either receptor. Angiotensin II values (RIA) were greater in diabetics (16.2 +/- 1.5 pg/ml vs 8.5 +/- 1.4 in controls; P less than 0.02) and concentrations of atrial natriuretic factor (RIA) were not significantly different. The data suggest increased angiotensin II binding despite high angiotensin II concentrations in non-nephropathic type I diabetic patients. These findings may be relevant when considering the evolution of hypertension and microangiopathy lesions.
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PMID:Specific binding of angiotensin II and atrial natriuretic factor in non-nephropathic type I diabetes mellitus. 252 55

Plasma renin activity (PRA) may be high among teenage and young adult insulin-dependent diabetic subjects. Supine PRA and stimulated PRA were therefore measured in 50 female and 50 male diabetic subjects, 13-20 years old, diagnosed before the age of 16. Fifty percent have been restudied after 4.6 +/- 0.2 (mean +/- SEM) years. Initially, 43% had high PRA (supine 4.0 +/- 0.37, stimulated 12.02 +/- 0.8 ng/ml/hr angiotensin I), 45% had normal activity (supine 2.89 +/- 0.26, stimulated 6.47 +/- 0.34 ng/ml/hr/angiotensin I), and 12% had low activity (supine 1.57 +/- 0.05, stimulated 3.09 +/- 0.08 ng/ml/hr/angiotensin I). Levels were directly associated with prepubertal duration of diabetes and were inversely associated with duration of diabetes after onset of puberty but not with total duration or patient age. Within 4.6 +/- 0.2 years the percentage of subjects with high PRA fell to 13%, and the percentage of those with low PRA rose to 35%. Initially 51% of the cohort had normal albumin excretion rates (AER) at rest and during exercise equal to or less than 10 micrograms/min/m2; 32% had elevated rates only during exercise of 39 +/- 5 micrograms/min/m2; 13% had elevated rates at rest of 41 +/- 8 micrograms/min/m2 and during exercise of 116 +/- 21 micrograms/min/m2; and 4% had clinical proteinuria at rest and during each exercise period equal to or greater than 150 micrograms/min/m2. After 5 years, 58% continued to have normal AER, or their AER improved.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma renin activity and albumin excretion in teenage type I diabetic subjects. A prospective study. 266 31

Hypertension is an important risk factor in the progression of renal failure, particularly in patients with pre-existing glomerulopathies such as diabetes and chronic glomerulonephritis. The mechanisms involved in hypertensive glomerular injury are currently unclear and cannot be studied in humans because of the constraints of human experimentation. However, recent animal studies have elucidated mechanisms which may explain the variable relationship between systemic hypertension and glomerular injury. Experimentally, at similar levels of systemic hypertension, glomerular injury only develops when preglomerular resistances are ineffective, thus allowing the development of glomerular hypertension. The mechanisms by which the haemodynamic stress of elevated intracapillary pressures and flows lead to progressive glomerular damage are at present unknown. Endothelial cell injury, increased mesangial traffic and/or trapping of macromolecules and epithelial cell injury appear to occur early, followed by in situ inflammatory and microthrombotic mechanisms. The intrarenal renin-angiotensin system appears to play an important role in the pathogenesis of progressive glomerular injury. Haemodynamically, angiotensin II (Ang II) has a relatively greater vasoconstrictive effect on efferent than on afferent arterioles. In addition, Ang II decreases the glomerular ultrafiltration coefficient. These combined effects result in increased intraglomerular capillary pressures. Angiotensin II increases the uptake and decreases the egress of circulating macromolecules in the glomerular mesangium and fosters mesangial cell mitogenesis. Thus, inhibition of Ang II generation may explain why angiotensin converting enzyme (ACE) inhibitors may be effective in arresting or slowing the progression of renal failure in experimental animals and in man.
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PMID:Possible mechanism for the renoprotective effect of angiotensin converting enzyme inhibitors. 269 55

The comparative effects of lisinopril, a third generation angiotensin converting enzyme (ACE) inhibitor, on components of the renin-angiotensin system were assessed in normal and in an animal model of diabetes-related hypertension, the streptozotocin-diabetic rat. Two weeks after injection of streptozotocin the mean systolic blood pressure of diabetic rats was elevated 11% above that of normal rats. This effect was prevented by daily injection of insulin. The mean serum ACE activity was elevated 71% above that of normal rats. Lisinopril reduced systolic blood pressure and inhibited serum ACE activity in both normal and diabetic rats in a dose-response fashion. In normal rats maximum inhibition of blood pressure occurred at a mean dose of 1.0 mg/kg and in the diabetic rat at a mean dose of 5.0 mg/kg. At a mean dose of 5 mg/kg, ACE was inhibited by 100 and 92% in normal and diabetic rats, respectively. Plasma renin activity (PRA) increased sharply in both groups of rats treated with the lower doses of lisinopril, only to decrease at the 5 mg/kg level. At 20 mg/kg, PRA continued to decline in normal animals, but not in diabetic rats. Formation of angiotensin II (Ang II) in both normal and diabetic rats was maximally inhibited at doses of 1.0 and 0.1 mg/kg of lisinopril, respectively without a significantly greater effect at the higher doses of the drug. In separate experiments the effects of chronic treatment with lisinopril at two dosage levels on various physiological parameters of streptozotocin-diabetic rats were compared with the effects of another hypotensive agent, hydralazine, an arteriolar vasodilator.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of the angiotensin converting enzyme inhibitor, lisinopril, on normal and diabetic rats. 284 85

Angiotensin-converting enzyme, the polypeptide that converts angiotensin I to angiotensin II, was measured in the serum of 114 pregnant women who had normal blood pressure, pregnancy-induced hypertension-preeclampsia, and chronic hypertension with or without pregnancy-induced hypertension. Angiotensin-converting enzyme levels were unrelated to weeks of gestation. The angiotensin-converting enzyme levels were similar in normotensive women (21.1 +/- 6.9 units/ml), women with chronic hypertension without pregnancy-induced hypertension (23.1 +/- 2.7 units/ml), and patients with pregnancy-induced hypertension where magnesium sulfate (22.6 +/- 8.7 units/ml) had been administered prior to angiotensin-converting enzyme assay, but these values were significantly less than those in patients with pregnancy-induced hypertension with no magnesium sulfate (29.1 +/- 6.5 units/ml) therapy and in women with chronic hypertension with superimposed pregnancy-induced hypertension (30.7 +/- 4.4 units/ml) (p less than 0.005). Maternal venous and umbilical venous and arterial angiotensin-converting enzyme levels were as follows: The maternal venous level was less than the cord venous level and greater than the cord arterial value. Neither neonatal size nor twin gestation influenced the angiotensin-converting enzyme levels. Patients with diabetes mellitus had variable angiotensin-converting enzyme values regardless of the status of the blood pressure. The physiologic theories of blood pressure control in pregnant women are discussed in relation to the renin-angiotensin, bradykinin, and prostaglandin systems.
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PMID:The relation of angiotensin-converting enzyme to the pregnancy-induced hypertension-preeclampsia syndrome. 300 58

Angiotensin II receptors on platelets were studied in 13 patients with uncomplicated type I diabetes mellitus and in 15 age-matched normal subjects. Receptor density on cells from the diabetic patients was 15% lower than the normal subjects (5.2 +/- 0.8 SD sites/platelet in diabetic patients and 6.4 +/- 0.8 in normals, P less than 0.001), but there were no differences in receptor affinity as measured by Kd (4.9 +/- 1.5 X 10(-10) mol/l in diabetic patients and 5.4 +/- 1.4 X 10(-10) mol/l in normals). Plasma concentrations of renin and angiotensin II were similar in both groups. The reduced density of angiotensin II receptors on platelets from patients with insulin-dependent diabetes may reflect a generalized abnormality of angiotensin II receptor regulation.
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PMID:Reduced number of angiotensin II receptors on platelets in insulin-dependent diabetes. 301 90

Renin and prorenin, the latter after conversion to renin, are usually measured by indirect RIA using antibodies against angiotensin I. They can now also be measured by direct RIA using monoclonal antibodies reacting with total immunoreactive renin (renin plus prorenin) or with renin alone. Results of measurements in renal and peripheral venous plasma indicate that normally a large proportion of prorenin in plasma is of renal origin and they support the concept of separate pathways for prorenin and renin secretion by the JG-cells. Acute stimulation causes a prompt increase of plasma renin without any change in prorenin. During chronic stimulation both renin and prorenin are increased, in such a way that the ratio between the two is higher the stronger the stimulus. Thus, with acute stimulation only the release of stored renin appears to be increased (regulated pathway), whereas during chronic stimulation the synthesis and secretion of prorenin are also (constitutive pathway). During pregnancy, in the early luteal phase of the menstrual cycle and after ovarian hyperstimulation with gonadotropins, a normal or somewhat elevated plasma level of renin is associated with a disproportionally high level of prorenin. This is an indication of extrarenal production of prorenin and in these conditions the ovary, probably corpus luteum, seems to be the main source. In most patients with renin-producing tumors plasma prorenin is also disproportionally high. In diabetes mellitus complicated by micro-angiopathy plasma prorenin is also elevated whereas renin is normal or even low. In diabetics with end-stage nephropathy we found no significant veno-arterial difference in prorenin across the kidneys, despite high circulating prorenin and a very low blood flow through these kidneys, suggesting that also in these patients part of the increased prorenin in plasma is of extrarenal origin. Thus, measurements of prorenin in plasma in various pathological conditions may contribute to a better understanding of the physiological role of the renal and extrarenal renin-angiotensin systems.
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PMID:Human prorenin: pathophysiology and clinical implications. 306 28


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