Low paraoxonase activity in type II diabetes mellitus complicated by retinopathy

2000 ◽  
Vol 98 (3) ◽  
pp. 355-363 ◽  
Author(s):  
Bharti MACKNESS ◽  
Paul N. DURRINGTON ◽  
Bashir ABUASHIA ◽  
Andrew J. M. BOULTON ◽  
Michael I. MACKNESS
Keyword(s):  
Lipid Peroxidation ◽  
Glycaemic Control ◽  
Type Ii Diabetes ◽  
Plasma Lipids ◽  
Density Lipoprotein ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Control Group ◽  
Type Ii ◽  
Serum Pon1 Activity

Human serum paraoxonase 1 (PON1) is located on high-density lipoprotein and has been implicated in the detoxification of organophosphates, and possibly in the prevention of lipid peroxidation of low-density lipoprotein. PON1 has two genetic polymorphisms, both due to amino acid substitutions: one involving glutamine (Q genotype) and arginine (R genotype) at position 192, and the other involving leucine (L genotype) and methionine (M genotype) at position 55. We investigated the effects of these polymorphisms, and of a polymorphism of the PON2 gene at position 310 (Cys/Ser; C and S genotypes respectively), on serum PON1 activity and concentration, plasma lipids and lipoproteins and glycaemic control in 93 individuals with type II diabetes with no complications and in 101 individuals with type II diabetes with retinopathy. Serum PON1 activity in the group with no complications [median 164.1 nmol·min-1·ml-1 (range 8.0–467.8)] was significantly higher than in the group with retinopathy [113.4 nmol·min-1·ml-1 (3.0–414.6)] (P< 0.001), but the serum PON1 concentration was not different between the groups. The gene frequencies of the PON1-55 and PON1-192 polymorphisms and of the PON2-310 polymorphism were not different between the study populations. The PON1-55 and PON1-192 polymorphisms affected PON1 activity in the way described in a previous study of a control group and subjects with type II diabetes. The PON2-310 polymorphism also significantly affected serum PON1. PON1 activity was significantly higher in individuals with the PON2-310 CC genotype in both groups with type II diabetes, and the PON1 concentration was significantly higher in PON2-310 CC homozygotes with no complications than in the group with retinopathy. Neither the PON1-55 nor the PON1-192 polymorphism was correlated with the serum lipid or lipoprotein concentration in either group. In the group with retinopathy (but not the group with no complications), all three PON polymorphisms were correlated with glycaemic control, which was worse for the PON1-55 genotypes in the order MM > LM > LL (P = 0.0032), for the PON1-192 genotypes in the order RR > QR > QQ (P = 0.011) and for the PON2-310 genotypes in the order CC > CS > SS (P = 0.010). Low serum PON1 activity in retinopathy may be related to an increased tendency for lipid peroxidation. Our findings thus raise the possibility that, in retinopathy, the PON2 gene may influence PON1, and that an inter-relationship between the PON1 and PON2 genes may influence glycaemic control in subjects with type II diabetes complicated by retinopathy.

Paraoxonase-1 (PON-1) genotype and activity and in vivo oxidized plasma low-density lipoprotein in Type II diabetes

2005 ◽  
Vol 109 (2) ◽  
pp. 189-197 ◽  
Author(s):  
Mike J. Sampson ◽  
Simon Braschi ◽  
Gavin Willis ◽  
Sian B. Astley
Keyword(s):  
Type Ii Diabetes ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Paraoxonase 1 ◽  
Ldl Oxidation ◽  
Phenyl Acetate ◽  
Low Density ◽  
Type Ii

The HDL (high-density lipoprotein)-associated enzyme PON (paraoxonase)-1 protects LDL (low-density lipoprotein) from oxidative modification in vitro, although it is unknown if this anti-atherogenic action occurs in vivo. In a cross-sectional study of 58 Type II diabetic subjects and 50 controls, we examined the fasting plasma LDL basal conjugated diene concentration [a direct measurement of circulating oxLDL (oxidatively modified LDL)], lipoprotein particle size by NMR spectroscopy, PON-1 polymorphisms (coding region polymorphisms Q192R and L55M, and gene promoter polymorphisms −108C/T and −162G/A), PON activity (with paraoxon or phenyl acetate as the substrates) and dietary antioxidant intake. Plasma oxLDL concentrations were higher in Type II diabetic patients (males, P=0.048; females, P=0.009) and unrelated to NMR lipoprotein size, PON-1 polymorphisms or PON activity (with paraoxon as the substrate) in any group. In men with Type II diabetes, however, there was a direct relationship between oxLDL concentrations and PON activity (with phenyl acetate as the substrate; r=0.611, P=0.0001) and an atherogenic NMR lipid profile in those who were PON-1 55LL homozygotes. Circulating oxLDL concentrations in vivo were unrelated to PON-1 genotypes or activity, except in male Type II diabetics where there was a direct association between PON activity (with phenyl acetate as the substrate) and oxLDL levels. These in vivo data contrast with in vitro data, and may be due to confounding by dietary fat intake. Male Type II diabetic subjects with PON-1 55LL homozygosity have an atherogenic NMR lipid profile independent of LDL oxidation. These data do not support an in vivo action of PON on LDL oxidation.

scholarly journals Reduced Paraoxonase 1 Activity as a Marker for Severe Coronary Artery Disease

2013 ◽  
Vol 35 ◽  
pp. 97-103 ◽  
Author(s):  
Chiyan Zhou ◽  
Jia Cao ◽  
Liang Shang ◽  
Chuanfeng Tong ◽  
Hanling Hu ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Atherosclerotic Lesion ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Control Group ◽  
Potential Biomarker ◽  
Artery Disease

Paraoxonase-1 (PON1), a high-density-lipoprotein- (HDL-) associated enzyme, has the potential to protect against atherogenesis. We examine the relationships between plasma PON1 activity and the progression of atherosclerosis as well as coronary artery disease (CAD). Fasting blood samples were collected from female apolipoprotein E-deficient (apoE−/−) mice and 149 patients undergoing coronary angiography for the biochemical parameters measurement. The severity of CAD was defined using angiographic Gensini score (GSS). Compared to 3-month-old apoE−/−mice, aged mice had significantly lower PON1 activity, which is negatively correlated with the size of atherosclerotic lesion and plasma interleukin-6 (IL-6) and tumor necrosis factorα(TNF-α) levels. In study patients, PON1 activity was correlated with age, sex, and HDL-cholesterol, apolipoprotein AI, and high-sensitivity C-reactive protein (hs-CRP) levels and was significantly lower in CAD group than that in non-CAD control group. Interestingly, PON1 activity in severe CAD group (GSS > 40) was further significantly reduced compared to those in mild and moderate subgroups (GSS  ≤ 40) (P<0.01). There is a significant correlation between PON1 activity and the severity of CAD as assessed by GSS (r=-0.393,P<0.001). PON1 activity may be a potential biomarker for the severity of CAD.

scholarly journals Evaluation of Serum HDL and LDL levels in Type II Diabetes Mellitus

2013 ◽  
Vol 1 (1) ◽  
pp. 21 ◽  
Author(s):  
K R Joshi ◽  
K K Hiremath ◽  
S P Gupta
Keyword(s):  
Diabetes Mellitus ◽  
Type Ii Diabetes ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Type Ii Diabetes Mellitus ◽  
Lipoprotein Cholesterol ◽  
Control Group ◽  
Type Ii

  Introduction: Diabetes mellitus is a type of metabolic disorder characterized by hyperglycemia resulting from defect in insulin secretion, insulin action or both. This study intended to compare High Density Lipoprotein Cholesterol (HDL) and Low Density Lipoprotein Cholesterol (LDL) profile between type II diabetic and non-diabetic subjects and also find the correlation between HDL and LDL cholesterol in type II diabetic.   Methods: The study was conducted on 100 total subjects out of which experimental group with 50 subjects of known Type II Diabetes mellitus and control group with 50 subjects.   Results: The result of the present study suggests that fasting blood sugar and LDL cholesterol levels were increased but HDL cholesterol level was reduced in type II diabetic subjects when compared to controls.   Conclusion: The estimation of HDL cholesterol and LDL cholesterol in type II diabetes mellitus is very useful as it may serve as a useful parameter to monitor the prognosis of the patient.

Glycaemic instability is an underestimated problem in Type II diabetes

2006 ◽  
Vol 111 (2) ◽  
pp. 119-126 ◽  
Author(s):  
Stephan F. E. Praet ◽  
Ralph J. F. Manders ◽  
Ruth C. R. Meex ◽  
A. G. Lieverse ◽  
Coen D. A. Stehouwer ◽  
...  
Keyword(s):  
Physical Activity ◽  
Blood Glucose ◽  
Glycaemic Control ◽  
Glucose Tolerance ◽  
Type Ii Diabetes ◽  
Whole Body ◽  
Control Group ◽  
Oral Glucose ◽  
Type Ii ◽  
Oral Glucose Tolerance

The aim of the present study was to assess the level of glycaemic control by the measurement of 24 h blood glucose profiles and standard blood analyses under identical nutritional and physical activity conditions in patients with Type II diabetes and healthy normoglycaemic controls. A total of 11 male patients with Type II diabetes and 11 healthy matched controls participated in a 24 h CGMS (continuous subcutaneous glucose-monitoring system) assessment trial under strictly standardized dietary and physical activity conditions. In addition, fasting plasma glucose, insulin and HbA1c (glycated haemoglobin) concentrations were measured, and an OGTT (oral glucose tolerance test) was performed to calculate indices of whole-body insulin sensitivity, oral glucose tolerance and/or glycaemic control. In the healthy control group, hyperglycaemia (blood glucose concentration >10 mmol/l) was hardly present (2±1% or 0.4±0.2/24 h). However, in the patients with Type II diabetes, hyperglycaemia was experienced for as much as 55±7% of the time (13±2 h over 24 h) while using the same standardized diet. Breakfast-related hyperglycaemia contributed most (46±7%; P<0.01 as determined by ANOVA) to the total amount of hyperglycaemia and postprandial glycaemic instability. In the diabetes patients, blood HbA1c content correlated well with the duration of hyperglycaemia and the postprandial glucose responses (P<0.05). In conclusion, CGMS determinations show that standard measurements of glycaemic control underestimate the amount of hyperglycaemia prevalent during real-life conditions in Type II diabetes. Given the macro- and micro-vascular damage caused by postprandial hyperglycaemia, CGMS provides an excellent tool to evaluate alternative therapeutic strategies to reduce hyperglycaemic blood glucose excursions.

scholarly journals Effects of high sucrose diet, gemfibrozil, and their combination on plasma paraoxonase 1 activity and lipid levels in rats.

2010 ◽  
Vol 57 (3) ◽  
Author(s):  
Marija Macan ◽  
Nada Vrkić ◽  
Ana Lucić Vrdoljak ◽  
Božica Radić ◽  
Vlasta Bradamante
Keyword(s):  
Control Diet ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Control Group ◽  
Lipid Levels ◽  
Sucrose Diet ◽  
High Sucrose Diet ◽  
The Relationship ◽  
High Sucrose ◽  
Serum Pon1 Activity

We investigated the influence of high sucrose diet (HSD) after 3 or 5 weeks of administration on paraoxonase 1 (PON1) activity in plasma of normolipidemic rats and the relationship between serum PON1 activity, triacylglycerides (TGs), HDL and total cholesterol vs. the control group of rats fed normal, control diet (CD). Because the data about the influence of gemfibrozil (GEM) on PON1 activity are controversial, we also investigated its effects (administration in the 4th and 5th week in rats on HSD and CD) on plasma PON1 activity and lipid levels in normolipidemic rats, and in rats with hypertriglyceridemia caused by HSD. Our results obtained in rats on HSD show a significant increase of plasma TGs levels by 47% (P

scholarly journals Paraoxonase-1 Enzyme Activity and Oxidative Status in Pulmonary Hypertension Original Article

2020 ◽  
Vol 19 (4) ◽  
pp. 652-658
Author(s):  
Muhsin Kalyoncuoglu ◽  
Murat Baskurt ◽  
Aysem Kaya ◽  
Gunes M Dogan ◽  
Okay Abacl ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pulmonary Hypertension ◽  
Medical Science ◽  
Paraoxonase 1 ◽  
Stress Index ◽  
Pon1 Activity ◽  
Control Group ◽  
Binary Logistic Regression Analysis ◽  
Healthy Controls ◽  
Serum Pon1 Activity

Objective: Oxidative stress has been considered to be one of the main causes for the development of pulmonary hypertension (PH) via leading alteration of pulmonary vasomotor tone induced by hypoxia. The aim of this study is to determine the serum paraoxonase-1 enzyme (PON-1) activity, arylesterase activity, the antioxidant-oxidant status in patients with PH and to compare with healthy controls. Material and Methods: Thirty five healthy ındividuals (mean age 45.7±5.9 years) as a control group and thirty eight patients (mean age 46.5±12.6 years) with a diagnosis of PH wereincluded in thestudy. Serum PON-1 and arylesterase activity, the total antioxidative capacity of plasma (TAC) and total oxidantstatus (TOS) were measured by using colorimetric methods. The Oxidative Stress Index (OSI) wascalculated as TOS/ TACX100. Results: Serum PON1 activity is significantly lower in PH patients when compared with healthy controls (p=0.001). The serum arylesterase activity and TAC, TOS and OSI status were similarin bothgroups. There is inverse correlation between serum PON1 activityand NYHA functionalcapacity (r:-0.649 p=0.001). Furthermore, PON1 activity of study patients are similarin the PH subgroups. Serum activity of PON1 wasfoundto bethe only independent parameter for the presence of PH in binary logistic regression analysis (OR 0.984, 95 % CI 0.977-0.992, p=0.001). Eight patients died follow up period (27.6±14.5 months) and none of theparametersincluding PON1 were associated with mortality. Conclusion: Serum PON1 activity of PH patients is lowerthanhealthypopulation, but does not predictmortality. Bangladesh Journal of Medical Science Vol.19(4) 2020 p.652-658

scholarly journals Investigation of paraoxonase 1 activity of the workers at the plant, who have long-term contact with organophosphorus compounds

2017 ◽  
Vol 15 (1) ◽  
pp. 57
Author(s):  
Natalia D Razgildina ◽  
Valentina V Miroshnikova ◽  
Aleksey V Fomichev ◽  
Ekaterina V Malisheva ◽  
Alexandra A Panteleeva ◽  
...  
Keyword(s):  
Enzymatic Activity ◽  
Organophosphorus Compounds ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Control Group ◽  
Pon1 Gene ◽  
Polymorphic Variants ◽  
Pon1 Polymorphisms ◽  
Serum Pon1 Activity

Background. Liver enzyme paraoxonase 1 (PON1) plays an important role in protection the organism from toxic effects of organophosphorus compounds (OPs) via their hydrolysis whose rate and efficiency depend on PON1 serum level activity. PON1 activity is largely determined by the polymorphic variants of the PON1 gene. Effect of long-term work with exposure to the toxic OPs on the PON1 activity is almost unknown. The aim of the present work was to study the effect of long-term work with exposure to the toxic OPs on PON1 serum enzymatic activity depending on polymorphisms Q191R, L54M, C(-108)T PON1 gene. Materials and methods. PON1 serum enzymatic activity and PON1 polymorphisms were determined in men, who were categorized in 2 groups: workers of companies providing storage and disposal of the OPs (68) and control group (37). The PON1 191, PON1 55 and PON1 108 polymorphisms were studied by polymerase chain reaction/restriction fragment length polymorphism. PON1 serum enzymatic activity was measured by a spectrophotometric method using paraoxon. Results. PON1 activity in workers with exposure to the toxic OPs relative was increased compared to the control group (p = 0,027). Differences in serum PON1 activity was shown for the carriers of certain genotypes of the PON1 gene: PON1 serum activity was higher in workers compared to controls only for LL genotype (L54M polymorphism) and C allele (C(-108)T polymorphism) carriers (p < 0,001 and p = 0,002, correspondently). Conclusion. We suggest that the increase in serum PON1 activity in workers providing storage and disposal of OPs could be modulated with the polymorphic variants of the PON1 gene.

scholarly journals Serum Paraoxonase 1 Activity Is Associated with Fatty Acid Composition of High Density Lipoprotein

2013 ◽  
Vol 35 ◽  
pp. 273-280 ◽  
Author(s):  
Maryam Boshtam ◽  
Amirnader Emami Razavi ◽  
Morteza Pourfarzam ◽  
Mohsen Ani ◽  
Gholam Ali Naderi ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid Composition ◽  
Fatty Acid ◽  
Stearic Acid ◽  
Acid Composition ◽  
Density Lipoprotein ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Healthy Men ◽  
Serum Pon1 Activity

Introduction. Cardioprotective effect of high density lipoprotein (HDL) is, in part, dependent on its related enzyme, paraoxonase 1 (PON1). Fatty acid composition of HDL could affect its size and structure. On the other hand, PON1 activity is directly related to the structure of HDL. This study was designed to investigate the association between serum PON1 activity and fatty acid composition of HDL in healthy men.Methods. One hundred and forty healthy men participated in this research. HDL was separated by sequential ultracentrifugation, and its fatty acid composition was analyzed by gas chromatography. PON1 activity was measured spectrophotometrically using paraxon as substrate.Results. Serum PON1 activity was directly correlated with the amount of stearic acid and dihomo-gamma-linolenic acid (DGLA). PON1/HDL-C was directly correlated with the amount of miristic acid, stearic acid, and DGLA and was inversely correlated with total amount ofω6 fatty acids of HDL.Conclusion. The fatty acid composition of HDL could affect the activity of its associated enzyme, PON1. As dietary fats are the major determinants of serum lipids and lipoprotein composition, consuming some special dietary fatty acids may improve the activity of PON1 and thereby have beneficial effects on health.

scholarly journals Arylesterase activity of paraoxonase 1 in patients with primary hypertension

2021 ◽  
Vol 75 (1) ◽  
pp. 859-867
Author(s):  
Aleksandra Baszczuk ◽  
Ewa Wysocka ◽  
Alicja Płóciniczak ◽  
Anna Thielemann ◽  
Anna Dżumak ◽  
...  
Keyword(s):  
Density Lipoprotein ◽  
Study Groups ◽  
Primary Hypertension ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Control Group ◽  
Newly Diagnosed ◽  
Laboratory Methods ◽  
Effect Of Therapy ◽  
Untreated Hypertension

Abstract Introduction Paraoxonase 1 is an enzyme associated with high-density lipoprotein fraction and is considered to present antioxidant activity. Objectives The aim of the study was to assess the arylesterase activity of paraoxonase 1 (PON1) in the serum of patients with hypertension, due to effect of therapy and before treatment. Patients and Methods. The study was conducted in 76 patients with primary hypertension and 28 volunteers for the control group. Hypertensive subjects were assigned to one of three groups: well controlled (n=25), poorly controlled (n=26), and newly diagnosed before therapy (n=25) hypertension. We evaluated metabolic parameters in all participants using routine laboratory methods, as well as arylesterase activity of PON1. Results The four study groups differed with arylesterase activity of PON1 and the highest levels were found in patients with well controlled hypertension and the lowest in newly diagnosed. All patients diagnosed with hypertension presented negative correlations between PON1 and systolic and diastolic blood pressure. Conclusions Effective treatment of hypertension could result in increased PON1 activity, despite unfavorable homocysteine concentrations in blood. Untreated hypertension might decrease activity of PON.

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