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)

Renal Kallikrein, an enzyme of the distal tubule acting through kinin liberation, may participate to the control of renal circulation and blood pressure. To study if an impairment of its secretion may exist in diabetics, a cross-sectional study was carried out on 40 non-hypertensive and 29 hypertensive diabetics, compared to 30-age related controls. Urinary Kallikrein Activity (UKA) was measured by its kininogenase activity with and without trypsin preincubation. Compared to UKA in controls (86 +/- 9 micrograms lysyl-bradykinin [LBK] produced per minute of incubation), UKA was significantly reduced either in non-hypertensive diabetics (59 +/- 8 micrograms LBK. min.-1; p less than 0.05) and in hypertensive diabetics (26 +/- 6 micrograms LBK. min.-1; p less than 0.001). The ratio of total/active urinary kallikrein was similar in diabetics and in controls. The decline of UKA in diabetics was related to the duration of their disease (r = -0.38; p less than 0.05) and to their stage of retinopathy (r = -0.46; p less than 0.001). UKA values were proportional to creatinine clearance in diabetics (r = 0.58; p less than 0.001). The lowest UKA values were found in patients with a high urinary excretion of albumin (above 500 mg/day): 8 +/- 2 micrograms LBK. min-1 (p less than 0.001) and beta-2-microglobulin (above 382 micrograms/day): 12 +/- 4 micrograms LBK. min-1 (p less than 0.001). These findings support that an impaired secretion of renal kallikrein in diabetics can be related to the duration of diabetes and to the severity of microangiopathy.
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PMID:[Reduction of urinary kallikrein in hypertensive diabetics]. 309 98

Cultured porcine aortic endothelial cells were conditioned through two passages to mimic euglycemic and hyperglycemic conditions (5.2 mM, normal glucose; 15.6 mM, elevated glucose). After incubation with 1 microM [14C]arachidonic acid for 24 h, the cells were stimulated with 1 microM A23187 for times up to 30 min. Uptake of [14C]arachidonic acid and its distribution among cell lipids were unaffected by the increased glucose concentration. The release of eicosanoids from labeled cells and unlabeled cells was measured by reverse-phase HPLC and by RIA, respectively. Compared with cells stimulated in the presence of normal glucose concentrations, cells stimulated in the presence of elevated glucose released 62.6% less free [14C]arachidonic acid, but released 129% more 14C-labeled 15-hydroxyeicosatetraenoic acid (HETE). Increased release of 15-HETE in the presence of elevated glucose in response to A23187, bradykinin, and thrombin was confirmed by RIA. A similar increase in 5-HETE release was observed by RIA after A23187 treatment. The release of both radiolabeled and unlabeled prostanoids was equal at both glucose concentrations. The data indicate that glucose may play an important role in the regulation of release and metabolism of arachidonic acid after agonist stimulation. In the presence of elevated glucose concentrations, such as those associated with diabetes mellitus, the extent and pattern of eicosanoid release from endothelial cells is markedly altered.
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PMID:Elevated glucose alters eicosanoid release from porcine aortic endothelial cells. 314 46

A tissue kallikrein was purified from rat skeletal muscle. Characterization of the enzyme showed that it has alpha-N-tosyl-L-arginine methylesterase activity and releases kinin from purified bovine low-Mr kininogen substrate. The pH optimum (9.0) of its esterase activity and the profile of inhibition by serine-proteinase inhibitors are identical with those of purified RUK (rat urinary kallikrein). Skeletal-muscle kallikrein also behaved identically with urinary kallikrein in a radioimmunoassay using a polyclonal anti-RUK antiserum. On Western-blot analysis, rat muscle kallikrein was recognized by affinity-purified monoclonal anti-kallikrein antibody at a position similar to that of RUK (Mr 38,000). Immunoreactive-kallikrein levels were measured in skeletal muscles which have different fibre types. The soleus, a slow-contracting muscle with high mitochondrial oxidative-enzyme activity, had higher kallikrein content than did the extensor digitorum longus or gastrocnemius, both fast-contracting muscles with low oxidative-enzyme activity. Streptozotocin-induced diabetes reduced muscle weights, but did not alter the level of kallikrein (pg/mg of protein) in skeletal muscle, suggesting that insulin is not a regulator of kallikrein in this tissue. Although the role of kallikrein in skeletal muscle is unknown, its localization and activity in relation to muscle functions and disease can now be studied.
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PMID:Identification and characterization of a tissue kallikrein in rat skeletal muscles. 331 Oct 22

Protein synthesis and degradation are particularly sensitive to malnutrition and catabolic states. Intracellular protein degradation is determined by the conformation, molecular weight, isoelectric point, and carbohydrate content of the proteins. ATP-stimulated endoproteases appear to catalyse the rate-limiting steps. In the liver, proteolysis is reduced by amino acids and/or insulin, whereas glucagon stimulates protein degradation, probably due to depletion of intracellular gluconeogenic amino acids. In the muscle, protein degradation is promoted by interleukin-1 and inhibited by Ep-475, which specifically inactivates cathepsin B,H, and L. Myofibrillar alkaline proteinase activity increases postoperatively and in patients suffering from malignant tumors, whereas normal proteinase values were observed in these patients following total parenteral nutrition. Increased alkaline proteinase activity is also observed in diabetes mellitus and is normalized by insulin. Extracellular proteolysis has been reported in patients with hypercatabolic acute renal failure and in patients with sepsis or acute pancreatitis. Plasma fractions obtained from hypercatabolic patients with postoperative acute renal failure were proteolytic. Plasma proteinase activity decreases during hemodialysis due to elimination of a metallo-proteinase. Plasma alpha 2-macroglobulin decreases in patients with acute renal failure and also during acute pancreatitis. Proteolytic degradation of parathyroid hormone by sera obtained from patients with acute pancreatitis has been observed. Also, there is a decrease of high molecular weight kininogen during experimental acute pancreatitis. Granulocyte elastase increases postoperatively, mainly in patients with sepsis. Sepsis also causes increased proteolytic activity in the urine. In conclusion, intracellular protein degradation can supply important precursors for hepatic and renal gluconeogenesis during malnutrition.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Proteinases in catabolism and malnutrition. 331

Alterations of plasma coagulation factors have been reported in diabetic patients with severe microangiopathy and metabolic derangement. No information is available, however, for well-controlled type-I diabetic patients. Thus, we studied coagulation factors of the contact phase and inhibitors in 80 fairly well-controlled diabetics (42 female, 38 male, age 28 +/- 11 SD years). Mean HbA1c in these patients was 6.6 +/- 1.0 SD, duration of diabetes ranged from 6 months to 30 years, and 36% had retinopathy shown by fluorescein angiography. The well-controlled diabetic patients did not differ from controls in terms of the activity of prekallikrein, factor XII, high molecular weight kininogen, kallikrein inhibitor, C-1-esterase inhibitor and antithrombin III. Only alpha-2-macroglobulin, an inhibitor of the contact phase of blood coagulation, was elevated significantly in these patients (p less than 0.05). Diabetics with retinopathy had similar activities of prekallikrein, factor XII, high molecular weight kininogen, kallikrein inhibitor, c-1-esterase inhibitor and antithrombin III when compared with patients without retinopathy and controls respectively. alpha-2-macroglobulin did not differ in patients with and without diabetic retinopathy but were significantly elevated in both groups compared with controls. Correlation analysis showed significant positive correlation between HbA1c and the activity of high molecular weight kininogen, kallikrein inhibitor and alpha-2-macroglobulin. In patients with poor metabolic control (n = 11; 6 female, 5 male; age 25 +/- 5 SD years; HbA1C 10.7 +/- 0.9) prekallikrein (p less than 0.05), kallikrein inhibitor (p less than 0.005) and alpha-2-macroglobulin (p less than 0.005) were significantly elevated compared to the controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes Res 1988 Apr
PMID:Coagulation factors of contact phase of haemostasis are normal in well-controlled type-I diabetic patients despite presence of diabetic retinopathy. 340 69

The aim of this study was to evaluate whether there are vascular alterations in diabetes prior to atherosclerotic lesions. Four and 12 weeks after induction of diabetes (streptozotocin, 60 mg/kg b.w.) in rats characterized by low plasma insulin, hyperglycaemia, glucosuria, and loss of body weight, however, without morphological alterations of the cardiac vasculature--local myocardial perfusion parameters were estimated in the epicardium of Langendorff perfused hearts using fluorescence indicator (FITC-dextrane, MG 3kD) washout kinetics after bolus injection. The elution profile was characterized by a fast vascular and a slow transendothelial component. In diabetic hearts, vascular as well as transendothelial washout were prolonged. Concomitantly, the vascular perfusion volume and the amount of indicator exchanged with the interstitium was significantly diminished. Vascular response to bradykinin (5 nmol/l) was moderately attenuated and the limitations in transendothelial indicator exchange could not be affected by bradykinin, although vascular perfusion volume was significantly increased. These findings clearly indicate disturbed local myocardial perfusion early in the development of diabetes.
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PMID:Early vascular alterations in the diabetic rat heart. 342 Nov 27

Abnormal pressor responses are known to occur in the maternal circulation in pregnancy-induced hypertension (PIH), but little is know of the response of the foetal circulation. The responsiveness of umbilical arteries in PIH can be studied after delivery, and this is a useful model to explore the pathophysiological mechanisms involved. In the present experiments, the in vitro response of umbilical artery rings to bradykinin and 5-hydroxytryptamine (5-HT) was tested and ultrastructural changes investigated. Umbilical arteries from 48 cords were studied. Fifteen of the mothers had PIH, five had essential hypertension pre-dating the pregnancy and five had diabetes. Twenty-three women had pregnancies uncomplicated by hypertension or serious medical or obstetric problems and these served as controls. Umbilical arteries from the severe proteinuric PIH group were significantly more responsive to 5-HT as assessed by affinity constants (P less than 0.05). The responsiveness of arteries from all other groups did not differ from the normal cases. A probable mechanism for the findings is endothelial damage as a result of pre-eclamptic disease. This was substantiated by ultrastructural evidence.
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PMID:Umbilical artery reactivity and ultrastructural changes in pregnancy-induced hypertension and other complicated pregnancies. 342 82

Studies were conducted to determine whether reduced renal blood flow (RBF) exhibited by rats with uncontrolled streptozotocin (STZ)-induced diabetes is attributable to diabetes-induced structural changes in the renal vasculature. Vehicle-treated control rats (CR) and rats that were injected with STZ (STZR) after pretreatment with 3-O-methylglucose (3-OMG), an agent that prevents STZ-induced hyperglycemia, were also studied. Basal values of total RBF (ml.min-1.g kidney wt-1, electromagnetic flow probe), systemic arterial pressure (BP, mmHg), and renal vascular resistance (RVR, BP/RBF) in pentobarbital-anesthetized rats during a control period were 5.4 +/- 0.3 (P less than 0.01 vs. CR), 116 +/- 3, and 21.9 +/- 1.0 (P less than 0.01 vs. CR) in STZR (n = 12) and 8.2 +/- 0.4, 121 +/- 2, and 15.3 +/- 1.0 in CR (n = 11), respectively. Basal values of RBF, BP, and RVR in 3-OMG-pretreated STZR were identical to CR. The relative capacity of STZR and CR kidneys for vasodilatation in situ in response to intrarenal arterial infusions of acetylcholine (ACh) and bradykinin (BK) and systemically administered sodium nitroprusside (NP) was evaluated. The capacity of STZR to exhibit active renal vasodilatation in response to intrarenal arterial ACh and BK was significantly less than that of CR (P less than 0.01). The minimum level to which RVR was suppressed after 50 micrograms NP/kg iv was higher in STZR than in either CR or 3-OMG-pretreated STZR (14.8 +/- 1.5 vs. 9.0 +/- 0.7 and 9.3 +/- 1.5 mmHg.ml-1.min.g kidney wt, respectively; P less than 0.05). This dose of NP exerted effective functional antagonism of renal vasoconstriction induced by exogenous norepinephrine and angiotensin II. These in vivo studies suggest that the elevated RVR in STZR might be attributable in part to structural changes in the renal vasculature that are associated with the diabetic state and limit the capacity for renal vasodilatation. However, there was no difference in pressure-flow relationships between the two groups in maximally dilated isolated kidneys perfused with Krebs buffer containing 5% albumin, and the RBF deficit in STZR kidneys was corrected by perfusion with blood from CR. Thus the decreased RBF exhibited by STRZ in vivo cannot be attributed solely to renal vascular structural changes associated with diabetes. These findings suggest that undefined humoral factors or abnormal interaction of formed blood elements with vessel walls may account for elevated RVR in STZR.
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PMID:Limited capacity for renal vasodilatation in anesthetized diabetic rats. 366 32

The contact phase has been studied in diabetics and patients with macroangiopathy. Factor XII and high molecular weight kininogen (HMWK) are normal. C1-inhibitor and also alpha 2-macroglobulin are significantly elevated in diabetics with complications, for alpha 2-macroglobulin especially in patients with nephropathy, 137.5% +/- 36.0 (p less than 0.001). C1-inhibitor is also increased in vasculopathy without diabetes 113.2 +/- 22.1 (p less than 0.01). Prekallikrein (PK) is increased in all patients' groups (Table 2) as compared to normals. PK is particularly high (134% +/- 32) in 5 diabetics without macroangiopathy but with sensomotor neuropathy. This difference is remarkable because of the older age of diabetics and the negative correlation of PK with age in normals.
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PMID:The contact phase of blood coagulation in diabetes mellitus and in patients with vasculopathy. 608 93

It has recently been observed that administration of bradykinin to diabetic patients improves peripheral glucose utilization. To verify whether there is an alteration of the kallikrein-kinin system in human diabetes, plasma kallikrein activity was measured in 47 diabetic patients and in 20 control subjects. In diabetics plasma kallikrein activity was significantly higher than in controls: 1.04 +/- 0.04 U/ml (p less than 0.001). Although they do not refute the hypothesis that there is an alteration of the kallikrein-kinin system in diabetes mellitus, these findings do not support such a hypothesis either. Increased synthesis of plasma kallikrein activity may be due to increased synthesis of carbohydrate-protein compounds in diabetes mellitus.
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PMID:Plasma kallikrein activity in human diabetes mellitus. 634 68


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