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)

Paraoxonase (PON1) is an antioxidant enzyme closely associated with high-density lipoproteins. Low PON1 has been shown in oxidative stress-associated processes such as dyslipidemia, diabetes mellitus, advancing age, and smoking. Indeed, oxidative stress is related to the degree of insulin resistance, a key component of the metabolic syndrome. Therefore, the possible relationship between PON1 activity and the metabolic syndrome was investigated. From 1364 randomly recruited subjects, 285 were found to have the metabolic syndrome, according to the guidelines published by the National Cholesterol Education Program, Adult Treatment Panel III. PON1 activity, lipid peroxides, and PON1 codon 192 genotypes, which strongly modulate PON1 activity, were determined. Serum PON1 activity levels were found to be significantly lower, and lipid peroxide concentrations significantly higher, in subjects with the metabolic syndrome compared with unaffected subjects (P = 0.033 and < 0.001, respectively). Study subjects showed a significant decreasing trend in PON1 activity levels and a significant increasing trend in lipid peroxide concentrations, with the increase in the number of metabolic disturbances. No differences in the prevalence of PON1 codon 192 genotypes were found among the categories of metabolic abnormalities. In conclusion, a greater degree of severity of the metabolic syndrome is associated with a progressively worse antioxidant/oxidant balance, which is consistent with increased oxidative stress and lower antioxidant PON1 enzymatic capacity.
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PMID:Antioxidant paraoxonase 1 activity in the metabolic syndrome. 1460 83

In a cross-sectional study, oxidative stress in high vascular disease risk groups, ESRD (end-stage renal disease) and Type I diabetes, was assessed by measuring plasma protein carbonyls and comparing antioxidant capacity of HDL (high-density lipoprotein) as pertaining to PON1 (paraoxonase 1) activity and in vitro removal of LPO (lipid peroxides). ESRD subjects on haemodialysis (n=22), Type I diabetes subjects (n=20) without vascular complications and healthy subjects (n=23) were compared. Plasma protein carbonyls were higher in ESRD patients [0.16 (0.050) nmol/mg of protein; P=0.001; value is mean (SD)] relative to subjects with Type I diabetes [0.099 (0.014) nmol/mg of protein] and healthy subjects [0.093 (0.014) nmol/mg of protein]. Plasma PON1 activity, with and without correction for HDL-cholesterol, was lower in diabetes but did not differ in ESRD compared with healthy subjects. Plasma PON1 activity, without correction for HDL, did not differ between the three groups. In ESRD, plasma PON1 activity and plasma protein carbonyl concentrations were inversely related (r=-0.50, P<0.05). In an in vitro assay, LPO removal by HDL in ESRD subjects was greater than HDL from healthy subjects (P<0.01), whereas HDL from patients with Type I diabetes was less effective (P<0.01). Efficacy of LPO removal was unrelated to plasma PON1 activity, in vitro glycation or mild oxidation, but was impaired by marked oxidation and glycoxidation. Protein carbonyl levels are increased in ESRD but not in complication-free Type I diabetes. HDL antioxidant function is increased in ESRD, perhaps a compensatory response to increased oxidative stress, but is lower in Type I diabetes. HDL dysfunction is related to glycoxidation rather than glycation or PON1 activity.
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PMID:Oxidative stress and high-density lipoprotein function in Type I diabetes and end-stage renal disease. 1563 92

Human serum paraoxonase (PON1) has been implicated to play an important role in cardiovascular disease and diabetes. Studies in the literature indicate that PON1 has two different enzyme activities, i.e., esterase and hydroperoxide reducing activities. The objective of this study was to establish the importance of these two activities and to distinguish between them. As the addition of copper immediately inactivated the enzyme, we used auto-oxidation as the model system. Auto-oxidation of HDL resulted in more than 80% reduction of the esterolytic activity, which was protected by antioxidants, Vitamin E (50%) and PDTC (95%) and completely by 1 M glucose. In contrast, the hydroperoxide reducing activity, using unesterified hydroperoxides remained unaffected with time. We also used pNPHPODE (novel substrate) to establish that hydrolysis might be a prerequisite for the enzyme to act on the esterified hydroperoxide. The results indicated that the hydrolysis of the substrate was inhibited under oxidizing conditions with no reduction of the hydroperoxide. Overall, our findings suggest that protecting the esterolytic activity of PON1 by antioxidants might be important in preserving its action on phospholipid peroxides and a concerted reaction involving the esterolytic and hydroperoxide reducing activities might be suggested for the action of PON1.
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PMID:Oxidative inactivation of paraoxonase--implications in diabetes mellitus and atherosclerosis. 1611 60

The aim of this study was to determine whether the paraoxonase (PON1) status, i.e. PON1 activities and phenotypes (AA, AB and BB), and its relationship with lipid status are different in patients with type II diabetes as compared to healthy population. Diabetic group comprised 175 patients with type II diabetes mellitus (94 men and 81 women) who came to their regular control examination and took the oral glucose tolerance test. Patients with type II diabetes mellitus diagnosis for 12 years on average were on peroral antidiabetics, or insulin or diet, and 3 patients had no therapy prescribed yet. Control group comprised 114 apparently healthy individuals (28 men and 86 women) who were not on any medication. The paraoxonase activity was measured with 2.0 mmol L(-1) paraoxon in the absence and in the presence of 1.0 mol L(-1) NaCl, and with 2.0 mmol L(-1) phenylacetate. Both activities were measured spectrophotometrically at 37 degrees C in 0.1 mol L(-1) Tris-HCl buffer, pH = 8.0, containing 2.0 mmol L(-1) CaCl(2). Sera of diabetic and control subjects were assigned to the paraoxonase phenotypes on the basis of the basal paraoxonase activity distribution. We assigned 45% sera of male and 49% sera of female diabetic patients, and 64% sera of both genders of the control group to the AA low activity phenotype. There were no differences in paraoxonase activities between the gender- and phenotype-matched diabetic and control groups. Enzyme activity against the phenylacetate was higher, and phenotype-dependent, only in diabetic patients. In contrast to AA phenotype individuals, total cholesterol and LDL-cholesterol in the female diabetic group and triglyceride concentration in the male diabetic group assigned to pooled AB and BB phenotypes were higher than in the corresponding controls. It follows from PON1 phenotype distribution that less antiatherogenic paraoxonase B allele is more frequent in type II diabetes mellitus than in the healthy population. Their lipid status is more atherogenic, which could indicate a risk of premature atherosclerosis.
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PMID:Paraoxonase/arylesterase in serum of patients with type II diabetes mellitus. 1661 35

Apolipoprotein (apo) J, clusterin, is ubiquitously expressed in many tissues, and is a component of high-density lipoproteins (HDLs). There is experimental evidence that it may be anti-atherogenic through its effects on cholesterol transport, smooth muscle cell proliferation and lipid peroxidation. HDLs containing apo J and apo A-I carry paraoxonase (PON1), which protects low-density lipoproteins from oxidative modification; however, the extent to which apo J affects coronary heart disease (CHD) is not known. We have developed a sandwich ELISA that enables apo J to be assayed in the range of 13-200 microg/mL. Serum apo J was 52.8+/-0.8 microg/mL (mean+/-SEM; range, 36.0-84.3 microg/mL; n=92) in healthy Japanese men, and 49.3+/-0.5 microg/mL (34.5-72.8; n=241) in healthy Japanese women. Multiple regression of these data and results from 67 men with CHD showed that apo J concentration was unrelated to age, sex or body mass index, but was positively related to serum PON1 (p<0.001) and apo B (p<0.02) concentrations. In women, it was also positively related to blood glucose (p<0.02). After adjusting for its associations with covariates, serum apo J averaged 5.4 microg/mL, lower in CHD men than in controls (p<0.003). Type 2 diabetics had higher apo J concentrations (men, 83.1+/-3.4 microg/mL, n=64; women, 64.0+/-2.3 microg/mL, n=46) than healthy men and women (p<0.001). In these Type 2 diabetics, apo J concentration was unrelated to PON1 concentration, but was positively related to blood glucose (p<0.01). After adjustment for its relation to blood glucose, the mean apo J concentration was similar in diabetics and healthy subjects. These findings suggest that apo J may be anti-atherogenic in humans, and that its concentration is raised by Type 2 diabetes.
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PMID:Serum apolipoprotein j in health, coronary heart disease and type 2 diabetes mellitus. 1719 96

The role of high-density lipoprotein associated paraoxonase (PON) 1 in protection against oxidative stress associated with the development of complications in diabetes mellitus has been reported. Variations in the PON1 gene, 55LM and 192QR have been described in different populations. These variations are known to be risk factors for heart disease, especially the L and R alleles. We have investigated the prevalence of both polymorphisms in the Malaysian population comprising the three major ethnic groups: Malay, Chinese and Indian, using polymerase chain reaction followed by restriction endonuclease digestion. The results show the pooled frequencies of L and R alleles were 0.91 and 0.54, respectively, similar to those in the Asian region. The frequency of the M allele was higher in Indians (p < 0.05), whereas the R allele was higher in both the Chinese and Malays compared to Indians (p < 0.05), indicating ethnic group-dependent genetic differences. The most common genotypic combination was LL/QR, followed by LL/RR. The genotype frequencies for the total Malaysian population showed a significant departure from Hardy-Weinberg equilibrium for the 55LM (p = 0.013) but not the 192QR (p = 0.056) polymorphisms. A strong linkage disequilibrium between L/55 and R/192 alleles was also observed. In the Malaysian population as a whole, Malays and Chinese showed a higher frequency of the R allele which is a risk factor for cardiovascular diseases.
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PMID:Ethnic variations in paraoxonase1 polymorphism in the Malaysian population. 1753 92

Paraoxonase (PON1) is a high-density lipoprotein (HDL)-associated enzyme that protects low-density lipoprotein (LDL) and HDL from peroxidation. In this study, PON1 activities were determined in patients with erectile dysfunction (ED) to investigate the relationship between ED and atherosclerosis. Forty patients, who had been diagnosed with ED by the medical and sexual anamnesis and routine laboratory tests, were included in the study. Thirty healthy, sexually active, married and age-matched men were selected as the control group. The patients and controls who underwent surgical or medical treatment in 1-week time and had a systemic disease such as malignancy, liver and renal insufficiency, and active infection and who smoked cigarettes were excluded. PON1 activities were measured spectrophotometrically. Unpaired samples t-test, correlation analyses and multiple linear regression analyses were used for statistical analyses. The results are given as mean+/-standard deviation of mean. The mean ages of the patient and the control groups were 31.05+/-6.90 (range 22-51) and 29.40+/-6.26 (range 19-46), respectively (P=0.307). Serum PON1 levels of the patient and the control groups were found to be 119.05+/-62.11 and 185.04+/-55.64, respectively. The difference between the groups was quite significant (P=0.001). Epidemiological and experimental studies indicate that PON1 activation was lower in individuals who had a tendency to develop atherosclerosis due to comorbidities such as diabetes, familial hypercholesterolemia and kidney disease. In this study, PON1 activity level was found to be significantly lower in ED patients than in control group. The decrease of PON1 activity may have a role in the ethiopathogenesis of ED, and the atherosclerosis development may be faster in the patients due to decreased activity of PON1, which is an antiatherogenic enzyme.
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PMID:Paraoxonase activity in patients with erectile dysfunction. 1778 55

The present study was designed to investigate the relationship between the serum levels of oxidant-antioxidant system (malondialdehyde (MDA) level, Paraoxonase (PON1) activity, nitric oxide (NO) level and superoxide dismutase (SOD) activity) and thyroid hormone status in hypothyroidism pre and posttreatment. The study group comprised 33 patients with primary hypothyroidism. 18 of these patients were reevaluated after euthyroid state i.e. at least 6 months of thyroxine replacement. The patients were compared with 26 normal healthy controls. Serum MDA level, PON1 activity, NO level and SOD activity were measured according to an enzymatic spectrophotometric method. MDA levels were found higher in patients with hypothyroidism before the treatment than the controls. MDA levels were also found to be decreased after the treatment in patients with hypothyroidism. However MDA were found still higher than the controls after the treatment. PON1 activity was found to be lower in patients pretreatment when compared to posttreatment hypothyroidism and controls. Posttreatment of hypothyroidism mean PON1 activity significantly increased compared to pretreatment level but it was still significantly lower than control level. NO level was higher in pretreatment hypothyroidism when compared to controls. SOD activity was not found different in patients before treatment when compared to controls. SOD activity was significantly higher in after treatment when compared to both pretreatment and control levels. In conclusion, increased ROS levels in hypothyroidism may result in a pro-oxidation environment, which in turn could result in decreased antioxidant PON1 activity, increased MDA and NO levels. As a result, lipid peroxidation may have a role in the pathogenesis of the atherosclerosis in hypothyroidism.
Exp Clin Endocrinol Diabetes 2007 Sep
PMID:Oxidative stress and enzymatic antioxidant status in patients with hypothyroidism before and after treatment. 1785 36

Diabetes Mellitus (DM) is a multisystemic disorder with serious complications and these patients may also have serious problems with their oral cavity probably because of the microangiopathic and neuropathic complications. In diabetic patients, there may be several problems of the oral cavity such as gingivitis, periodontitis, candidiasis, glossitis, oral ulcerations, loss of taste sensations, opportunistic infections and several other conditions dependent on these. One of the recent theories about complications in DM is the contribution of reactive oxygen radicals. Paraoxonase (PON1) is an enzyme that is synthesized in liver and having the capability of hydrolasing the active metabolite of an insectisid, parathion. Previously it was shown that there are two polymorphic areas on the PON1 gene: one causing a Leu --> Met substitution at 55th position, the other causing Gln --> Arg at the 192nd position. We investigated the differences in PON activities related to the oral lesions in Type 2 diabetics and control subjects to see their relationships with PON1 activity levels and the two main gene polymorphisms of PON1 genes, PON1 192 and PON1 55. We had 51 patients and 53 healthy subjects used in the study. PON activity was significantly decreased in Type 2 DM group compared to the control group. Neither PON1 192 nor PON1 55 genotypes had any differential effect on PON1 enzyme activity levels in either group. However, we found that PON1 55 M allele carriers had greater risk for general periodontal and/or gingival problems.
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PMID:The relationship of oral disturbances of diabetes mellitus patients with paraoxonase gene polymorphisms. 1900 35

Allelic variants of CYP1A1 and PON1 have been extensively studied as susceptibility factors in toxic response, although little is known about the role of these variants as risk factors for the plethora of diseases appearing in the human population. In this study we investigated the hypothesis of correlation of CYP1A1 and PON1 enzymes with the incidence of various medical examination findings in a Greek rural population professionally exposed to a variety of pesticides. The medical history of 492 individuals, randomly selected for the total population of 42,000, was acquired by interviews and their genotype determined for the CYP1A1*2A, PON1 M/L and PON1 Q/R polymorphisms. The assessment of exposure to pesticides of the population was verified by analytical methods. Analysis of the genetic data revealed that the allele frequencies of PON1 R, M and CYP1A1*2A alleles were 0.243, 0.39 and 0.107 respectively. The CYP1A1*2A polymorphism was found to have significant association with chronic obstructive pneumonopathy (p=0.045), peripheral circulatory problems (trend p=0.042), arteritis (p=0.022), allergies (trend p=0.046), hemorrhoids (trend p=0.026), allergic dermatitis (p=0.0016) and miscarriages (p=0.012). The PON1 Q/R polymorphism was found to have significant association with hypertension (p=0.046) and chronic constipation (p=0.028) whereas, the L/M polymorphism, with diabetes (p=0.036), arteritis (trend p=0.022) and hemorrhoids (trend p=0.027). Our results demonstrated an association between the CYP1A1/PON1 polymorphisms and several medical examination findings, thus indicating the possible involvement of the human detoxification system to health effects in a rural population exposed professionally to pesticides.
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PMID:Relation of PON1 and CYP1A1 genetic polymorphisms to clinical findings in a cross-sectional study of a Greek rural population professionally exposed to pesticides. 1902 66


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