Modulation by blood glucose levels of activity and concentration of paraoxonase in young patients with type 1 diabetes mellitus

Kordonouri, Olga; James, Richard; Bennetts, Bruce; Chan, Albert; Kao, Yan-Lin; Danne, Thomas; Silink, Martin; Donaghue, Kim C.

doi:10.1053/meta.2001.23291

Cited by 44 publications

(30 citation statements)

References 15 publications

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“…Our findings suggest that highexpressor alleles and a higher enzymatic activity are associated with increased susceptibility to microvascular complications (8,9,11). One explanation could be that although paraoxonase hydrolyzes harmful lysolipids produced by peroxidation, it might also increase their production from phospholipid peroxidation products and create a more harmful lipoprotein profile.…”

Section: Discussionmentioning

confidence: 81%

“…Hyperglycemia may influence the in vivo concentration and in vitro activity of PON1. Kordonouri et al (11) showed that higher PON1 activity was associated with high glucose levels but not with A1C. With adjustment for blood glucose and diabetes duration, PON1 activity was higher in subjects with different stages of retinopathy versus those without retinopathy.…”

Section: Discussionmentioning

confidence: 96%

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Association Between p.Leu54Met Polymorphism at the Paraoxonase-1 Gene and Plantar Fascia Thickness in Young Subjects With Type 1 Diabetes

et al. 2008

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OBJECTIVE -In type 1 diabetes, plantar fascia, a collagen-rich tissue, is susceptible to glycation and oxidation. Paraoxonase-1 (PON1) is an HDL-bound antioxidant enzyme. PON1 polymorphisms have been associated with susceptibility to macro-and microvascular complications. We investigated the relationship between plantar fascia thickness (PFT) and PON1 gene variants, p.Leu54Met, p.Gln192Arg, and c.-107CϾT, in type 1 diabetes. RESEARCH DESIGN AND METHODS-This was a cross-sectional study of 331 adolescents with type 1 diabetes (162 male and 169 female). PFT was assessed by ultrasound, PON1 was assessed by genotyping with PCR and restriction fragment-length polymorphism, and serum PON1 activity was assessed by rates of hydrolysis of paraoxon and phenylacetate.RESULTS -Median (interquartile range) age was 15.4 (13.5-17.3) years, and diabetes duration was 7.6 (4.9 -10.6) years. The distribution of p.Leu54Met genotypes was LL 135 (40.8%), ML 149 (45%), and MM 47 (14.2%). PFT was abnormal (Ͼ1.7 mm) in 159 adolescents (48%). In multivariate analysis, predictors of abnormal PFT were ML/LL versus MM p. CONCLUSIONS -Thickening of the plantar aponeurosis occurs predominantly in overweight and male adolescents with type 1 diabetes. The MM genotype at PON1 p.Leu54Met is associated with a reduced risk of abnormal PFT.

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Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 96%

Association Between p.Leu54Met Polymorphism at the Paraoxonase-1 Gene and Plantar Fascia Thickness in Young Subjects With Type 1 Diabetes

et al. 2008

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“…Among the numerous antioxidant enzymes, we focused in the present study on the thiolactonase activities which were decreased in the diabetic patients. Most studies evaluated the paraoxonase activity in Type I and Type II diabetic patients and found a decreased activity in these patients (Boemi et al, 2001;Kordonouri et al, 2001;Letellier et al, 2002;Mackness B et al, 1998;Agachan et al, 2004). Paraoxonase is a multifunctional antioxidant enzyme that not only can detoxify paraoxon, destroy oxidized low-density lipoprotein (ox-LDL) but also can hydrolyze homocysteine thiolactone.…”

Section: Discussionmentioning

confidence: 99%

Interactions Between Total Plasma Homocysteine, Oxidized LDL Levels, Thiolactonase Activities and Dietary Habits in Tunisian Diabetic Patients

Koubaa¹,

Smaoui²,

Mehri³

et al. 2011

Role of the Adipocyte in Development of Type 2 Diabetes

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“…The reasons for these discrepancies are not obvious but could be caused by differences in study populations, number of subjects studied, or diabetes control. The latter may be particularly important because glycation of HDL appears to inhibit PON1 activity (25), which may explain the distorted PON1 activity-to-mass ratio found in the patient groups, and therefore the worse the glycemic control, the more glycation and the less PON1 activity (26), leading to a decreased ability to metabolize oxidized LDL. However, the PON1 polymorphisms also appear to play a role in the metabolism of plasma oxidized LDL in our study.…”

Section: Discussionmentioning

confidence: 99%

Defective Metabolism of Oxidized Phospholipid by HDL From People With Type 2 Diabetes

Mastorikou

Mackness

2006

Diabetes

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HDL protects against atherosclerosis development. Defective functioning of HDL in type 2 diabetes may be one cause of increased cardiovascular disease associated with type 2 diabetes. HDL modulates LDL oxidation through the action of paraoxonase-1 (PON1), which is one of the major mechanisms by which HDL is antiatherogenic. We have compared the ability of HDL from people with type 2 diabetes (n ‫؍‬ 36) with no coronary heart disease (CHD) to metabolize oxidized palmitoyl arachidonyl phosphatidylcholine (ox-PAPC), a major product of LDL oxidation and a PON1 substrate, with that of HDL isolated from healthy control subjects (n ‫؍‬ 19) and people with CHD but no diabetes (n ‫؍‬ 37). HDL from people with type 2 diabetes metabolized 11% less ox-PAPC, and HDL from people with CHD metabolized 6% less, compared with HDL from control subjects (both P < 0.01). The ability of HDL from control and type 2 diabetic subjects containing the PON1-192RR alloform to metabolize ox-PAPC was significantly reduced compared with PON1-192QQ or QR genotypes (P < 0.05). The defective ability of HDL to metabolize ox-PAPC was reflected in a significant increase in circulating plasma oxidized LDL concentration in the two patient groups (37 ؎ 5, 53 ؎ 7, and 65 ؎ 7 mmol/l for control, CHD, and type 2 diabetic subjects, respectively; P < 0.001), with PON1-192RR genotype carriers having the highest concentrations. In the control group, there was a significant negative correlation between serum PON1 activity and oxidized LDL concentration (r ‫؍‬ 0.856, P < 0.001); however, this correlation was not evident in the patient groups. HDL from type 2 diabetic subjects without CHD had a decreased ability to metabolize oxidized phospholipids, which could lead to increased susceptibility to develop cardiovascular disease. Diabetes 55: 3099 -3103, 2006 T he oxidation of LDL in the artery wall is believed to be the primary event leading to the initiation and progression of atherosclerosis (1,2). HDL, on the other hand, is protective against the development of atherosclerosis (3,4). The primary protective effect of HDL was believed to be its pivotal role in reverse-cholesterol transport; however, HDL also has antioxidative, anti-inflammatory, and antithrombotic properties (5).HDL-associated paraoxonase-1 (PON1) is primarily responsible for the antioxidative properties of HDL in retarding the oxidation of LDL (6 -10). By modulating the oxidation of LDL, PON1 abolishes the oxidized LDLstimulated induction of monocyte-chemotactic protein-1 (MCP-1) production by endothelial cells, thereby preventing monocyte-endothelial cell interaction in one of the earliest processes of atherosclerosis (11,12). PON1 is low in patients with diabetes (13-15), leading to dysfunctional HDL with impaired antioxidant capacity (15). In type 2 diabetes, there is an inverse relationship between PON1 activity and circulating oxidized LDL levels (16,17), indicative of the major role of PON1 in retarding LDL oxidation. We have recently shown that adenovirus-mediated overexpression of hu...

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Modulation by blood glucose levels of activity and concentration of paraoxonase in young patients with type 1 diabetes mellitus

Cited by 44 publications

References 15 publications

Association Between p.Leu54Met Polymorphism at the Paraoxonase-1 Gene and Plantar Fascia Thickness in Young Subjects With Type 1 Diabetes

Association Between p.Leu54Met Polymorphism at the Paraoxonase-1 Gene and Plantar Fascia Thickness in Young Subjects With Type 1 Diabetes

Interactions Between Total Plasma Homocysteine, Oxidized LDL Levels, Thiolactonase Activities and Dietary Habits in Tunisian Diabetic Patients

Defective Metabolism of Oxidized Phospholipid by HDL From People With Type 2 Diabetes

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