Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study examined the effect of gliclazide on tissue-type plasminogen activator (t-PA)-related fibrinolysis in 23 Type I diabetic patients without residual beta-cell function and 17 Type II diabetic patients initially treated with tolbutamide. The Type I diabetic patients received gliclazide for a period of 6 months; the Type II diabetic patients were shifted from tolbutamide to gliclazide. In Type I diabetic patients, after 2-3 months of treatment with gliclazide, we observed a significant increase in plasma concentrations of total t-PA antigen that remained stable until discontinuation of the drug (p less than 0.0002), whereas the plasma concentrations of plasminogen activator inhibitor (PAI) did not change significantly during the study. Next, we investigated the possibility of gliclazide inducing t-PA-related fibrinolysis in a subset of Type II diabetics without detectable concentrations of t-PA during treatment with tolbutamide. The concentrations of active t-PA increased significantly 3 months after a change in treatment to gliclazide, and active t-PA again decreased in one patient to undetectable levels after 12 months with gliclazide. Moreover, the plasma concentrations of total t-PA antigen increased significantly (p less than 0.02) in this group of diabetic patients while PAI remained unchanged. The changes in t-PA-related fibrinolysis could not be related in either Type I or Type II diabetics to changes in metabolic state evaluated by blood glucose, HbA1c, cholesterol, triglycerides, or apolipoproteins A and B. We conclude that gliclazide has the potential to exert extrametabolic non-insulin-mediated effects on t-PA-related fibrinolysis in diabetic patients.
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PMID:Increased fibrinolytic potential induced by gliclazide in types I and II diabetic patients. 190 83

During treatment with tolbutamide 10 maturity onset diabetic patients had no detectable activity of tissue-type plasminogen activator (t-PA) determined on two occasions 3 months apart. All 10 patients responded on the change in treatment to gliclazide with an increase in activity of t-PA. However, after 12 months of treatment the t-PA activity in one of the 10 patients returned to the baseline level, whereas the remaining nine patients had a sustained increased t-PA activity compared to the period during treatment with tolbutamide. The concentration in plasma of t-PA antigen under basal conditions and after stimulation (venous occlusion) increased significantly during the period of treatment with gliclazide. The plasma concentrations of plasminogen activator inhibitor remained unchanged throughout the study. In contrast to these findings seven patients with marked activities of t-PA during treatment with tolbutamide retained unchanged levels of the variables reported above after a change in treatment to gliclazide. Serum glucose, HBA1c, apolipoproteins A and B, and triglycerides remained constant throughout the study, whereas serum cholesterol showed a decrease in both groups of patients after 3 months (P less than 0.05) as well as after 12 months (P less than 0.05) of treatment with gliclazide. There was no significant relationship between serum cholesterol concentrations and plasma concentrations of t-PA antigen indicating that the increase in t-PA antigen was independent of the metabolic state of the patients.
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PMID:Rise of plasma t-PA fibrinolytic activity in a group of maturity onset diabetic patients shifted from a first generation (tolbutamide) to a second generation sulphonylurea (gliclazide). 249 55

The effects of sulfonylureas on the production of plasminogen activator (PA) and antiactivator (PAI) were investigated using bovine aortic endothelial cells. All compounds studied stimulated PA release (1.3- to 5.2-fold), with glipizide being the most potent, followed by tolazamide, chlorpropamide, and tolbutamide, in that order, while glyburide was the least effective. Both tissue-type and urokinase-type PA production was enhanced. Studies using metabolic inhibitors indicated that both RNA and protein syntheses are required for the sulfonylurea-mediated stimulation of PA release. In addition to continuous release of the two PAs, there was also a continuous release of a single PAI, which did not show an increase after the sulfonylureas. These results suggest that, in addition to their beneficial effects in the treatment of diabetes mellitus, some sulfonylurea compounds may also have significant thrombolytic effects. These results also suggest that pharmacological enhancement of PA production by vascular endothelial cells may be a promising antithrombotic mechanism.
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PMID:Effects of sulfonylureas on the synthesis and secretion of plasminogen activator from bovine aortic endothelial cells. 312 27

An increased risk of ischemic heart disease in men with the Lewis blood group phenotype Le(a-b-) has been reported. It has been suggested that the Le(a-b-) phenotype is a genetic marker of the insulin resistance syndrome. To examine whether Le(a-b-) confers the insulin resistance syndrome, we studied a random sample of unrelated healthy young white men and women living in Copenhagen (n = 380, 18 to 32 years). All individuals had their insulin sensitivity estimated using Bergman's minimal model (intravenous glucose in combination with tolbutamide) and systolic blood pressure (SBP) was measured with a London School of Hygiene Sphygmomanometer. A number of anthropometric measurements including body mass index (BMI, kilograms/meters squared) and biochemical characteristics were performed. The Lewis blood group typing was carried out on erythrocytes. Twenty-one men had the Le(a-b-) phenotype. Compared to all other men (N = 165), the Le(a-b-) men had a significantly higher SBP (6 mm Hg, P = .0024). They also had higher values of BMI (8%, P = .016), total body fat mass (25%, P = .015), fasting values of serum insulin (32%, P = .006), serum C-peptide (20%, P = .029), and plasma glucose (8%, P = .003). The fasting values of serum lipids, plasminogen activator inhibitor (PAI-1) activity, tissue plasminogen activator (t-PA) antigen, and insulin sensitivity did not differ between Le(a-b-) men and men with other Lewis phenotypes. Altogether 194 women participated in the study of which 21 women had the Le(a-b-) phenotype. Except for a lower PAI-1 activity (45%, P = .044), no values differed between Le(a-b-) women and women with other Lewis phenotypes. The women were also stratified according to use of oral contraceptives. Le(a-b-) women using oral contraceptives (N = 8) had a significantly lower plasma level of fasting PAI-1 activity (P = .029) and t-PA antigen (P = .004) compared to women using oral contraceptives without the Le(a-b-) phenotype (N = 42). Our data support the hypothesis that Le(a-b-) men exhibit features of the insulin resistance syndrome, including higher levels of BMI, SBP, and fasting levels of serum insulin and plasma glucose. In young women no signs of the insulin resistance syndrome were found in subjects with the Le(a-b-) phenotype.
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PMID:Lewis phenotypes and the insulin resistance syndrome in young healthy white men and women. 855 28

Several haemostatic abnormalities are associated with proliferative diabetic retinopathy. While abnormalities in plasma fibrinolytic activity have been described in diabetic retinopathy, platelets (a rich source of plasminogen activator inhibitor type 1, PAI-1) have received little attention. As a result, little is known about the fibrinolytic potential of circulating whole blood in diabetic retinopathy. The concentrations of tissue-type plasminogen activator (t-PA) and of its fast-acting inhibitor. PAI-1 were measured in plasma from eight patients with type 1 diabetes complicated by proliferative retinopathy, and from eight patients with type 1 diabetes and background or no retinopathy, matched for age, sex and duration of diabetes. The concentration of PAI-1 in platelets was also measured. The ratio of t-PTA to PAI-1 in plasma was significantly higher in patients with proliferative retinopathy than in those without (0.66 vs. 0.37, p < 0.02). The average quantity of PAI-1 per platelet was significantly lower in the group with proliferative retinopathy (0.33 vs. 0.50 ng/10(6) platelets, p < 0.02). These data suggest that among patients with type 1 diabetes, total circulating fibrinolytic potential is higher in those with proliferative retinopathy.
Acta Diabetol 1999 Sep
PMID:Circulating tissue-type plasminogen activator and plasminogen activator inhibitor type 1 in proliferative diabetic retinopathy: a pilot study. 1066 20

Decreased plasma fibrinolysis may contribute to accelerated atherothrombosis in diabetes. To observe whether hyperglycemia and hyperinsulinemia, common findings in type 2 diabetes, acutely affect plasma fibrinolysis in vivo, we evaluated plasma fibrinolysis (lysis of fibrin plates, free PAI-1 activity and t-PA activity) in the rat after a hyperglycemic euinsulinemic clamp (n=8), an euglycemic hyperinsulinemic clamp (n=7) or a saline infusion (n=15). Plasma fibrinolytic activity was sharply reduced after both the hyperglycemic and hyperinsulinemic clamps as compared to the respective controls (mean lysis areas on the fibrin plate, 139+/-21 vs. 323+/-30 mm2, p<0.001; 78+/-27 vs. 312+/-27 mm2 p<0.001, respectively). Plasma PAI-1 activity was greater after both hyperglycemic and hyperinsulinemic clamps as compared to saline infusion (6.6+/-2.6 vs. 1.6+/-0.6 IU/ml, p<0.001; 26+/-4 vs. 1.3+/-0.7 IU/ml, p<0.0001, respectively). Plasma t-PA activity was significantly reduced both after the hyperglycemic (0.36+/-0.15 vs. 2.17+/-0.18 IU/ml in controls, p<0.001) and the hyperinsulinemic (0.3+/-0.1 vs. 2.3+/-0.3 IU/ml in control, p<0.001) clamps. These data show that in vivo both acute hyperglycemia and acute hyperinsulinemia can decrease plasma fibrinolytic potential and that this is due to increased plasma PAI-1 and decreased free t-PA activities.
Acta Diabetol 2001
PMID:Acute hyperglycemia and acute hyperinsulinemia decrease plasma fibrinolytic activity and increase plasminogen activator inhibitor type 1 in the rat. 1175 4

The inflammatory marker, C-reactive protein (CRP) is associated with long-term cardiovascular events. The aim of the study was to investigate the factors contributing to serum CRP, assess the relationship between CRP level and the parameters of visceral obesity, and examine the association between leptin and CRP level in type 2 diabetic patients. 150 patients with type 2 diabetes were enrolled. These patients were recently diagnosed (< or =3 years) with type 2 diabetes and were drug naive or taking sulfonylureas only. BMI, WC, and serum concentration of CRP, glycosylated hemoglobin (HbA1c), glucose, lipids, plasminogen activator-1 (PAI-1) and leptin were measured. Insulin resistance was estimated by the insulin resistance index of homeostasis model assessment (HOMA-IR). We measured the carotid intima-media thickness (IMT). Fat mass assessed by dual-energy X-ray absorptionmetry and abdominal fat distribution was determined by CT scan. Serum concentration of CRP was significantly correlated with BMI (gamma = 0.257, P < 0.01), WC (gamma = 0.293, P < 0.01), fat mass (gamma = 0.213, P < 0.01), total adipose tissue (gamma = 0.263, P < 0.01), visceral adipose tissue (gamma = 0.296, P < 0.01), insulin (gamma = 0.189, P = 0.047), PAI-1 (gamma = 0.206, P < 0.01), leptin (gamma = 0.322, P < 0.01), mean IMT (gamma = 0.132, P = 0.042), and HOMA-IR (gamma = 0.172, P = 0.045). After adjustment for age and gender, multiple regression analysis showed that serum CRP was significantly associated with leptin (beta = 0.326, P = 0.01) and visceral adipose tissue (beta = 0.265, P = 0.035). In conclusion, serum CRP level is significantly associated with obesity, especially the visceral adipose tissue, and serum leptin is another important independent factor associated with CRP in Korean type 2 diabetic patients.
Acta Diabetol 2010 Jun
PMID:Visceral adiposity and leptin are independently associated with C-reactive protein in Korean type 2 diabetic patients. 1941 64

Relationship between serum vascular endothelial growth factor (VEGF) level and parameters of endothelial injury and/or dysfunction in patients with diabetes mellitus type 2 with or without microalbuminuria was investigated. Eighty-four diabetic patients were divided in two subgroups (42 each): normoalbuminuric (NAU) and microalbuminuric (MAU). Forty-two blood donors were in control group. Serum VEGF and plasma von Willebrand factor, soluble thrombomodulin, plasminogen activator inhibitor 1, thrombin-activatable fibrinolysis inhibitor (TAFI) and tissue plasminogen activator (t-PA) were measured using enzyme-linked immunosorbent assay in all subjects. VEGF was significantly higher in NAU compared to controls. The difference between MAU and controls was not statistically significant, but there was a trend toward significance. Only TAFI correlated with VEGF in MAU. An observed significant increase of serum VEGF level already in NAU suggests that serum VEGF could be a sensitive predictor of endothelial dysfunction in type 2 diabetes.
Acta Diabetol 2010 Jun
PMID:Circulating vascular endothelial growth factor in the normo- and/or microalbuminuric patients with type 2 diabetes mellitus. 1943 48