leukotriene-b4 and Diabetes-Mellitus--Type-2

To examine the effect of n-3 polyunsaturated fatty acid supplements on the monocyte surface expression of adhesion molecules involved in proatherogenic monocyte-endothelial interactions, and on pro-inflammatory mediators in Type 2 diabetes mellitus.. Twenty-nine subjects with Type 2 diabetes and 21 controls without diabetes were studied. Monocyte expression of leucocyte function-associated antigens 1 and 3, intercellular adhesion molecule-1, and the major histocompatibility complex class II molecule HLA-DR were measured using a laser flow cytometric method. Supplementation with 2.08 g n-3 fatty acids for 21 days was undertaken and measurements repeated. Plasma soluble adhesion molecule concentrations, plasminogen activator inhibitor-1 activity and antigen and pro-inflammatory mediators (cysteinyl leukotriene and monocyte leukotriene B4) were also measured.. Groups did not differ in monocyte expression of adhesion molecules or HLA-DR, or in leukotriene production although plasma soluble adhesion molecule concentrations were higher in the diabetes groups (P<0.05). n-3 fatty acid supplementation influenced neither the expression of these molecules nor plasma soluble adhesion molecule concentrations or leukotriene production.. This study does not support increased monocyte adhesion molecule expression or abnormal monocyte production of pro-inflammatory mediators as mechanisms for increased atherogenic risk in Type 2 diabetes. Cardioprotective actions of n-3 fatty acids may not be mediated through these mechanisms.

Topics: Blood Platelets; CD58 Antigens; Diabetes Mellitus, Type 2; Dietary Supplements; England; Fatty Acids, Nonesterified; Fatty Acids, Omega-3; HLA-DR Antigens; Humans; Inflammation; Intercellular Adhesion Molecule-1; Leukotriene B4; Lymphocyte Function-Associated Antigen-1; Male; Middle Aged; Monocytes; Plasminogen Activator Inhibitor 1; Reference Values; White People

Diabetes is associated with an accelerated development of atherosclerosis. Specific mechanisms related to diabetes and hyperglycemia may play a role in this process. In particular, alterations of arachidonic acid (AA) metabolism have been reported. Our main goal was to investigate for differences in the concentration of LTB4 and RvD1 as well as selected cyclooxygenase-derived mediators in carotid plaques from diabetic and non-diabetic patients. We also aimed to analyze the relationship between omega 6 and omega 3 Poly-Unsaturated Fatty acids (PUFAs) content in the plaques and the concentrations of these lipid mediators.. 29 type 2 diabetic patients and 30 control patients admitted for surgical treatment of carotid stenosis were enrolled in the present study. Carotid plaques were harvested for in-depth lipidomic profiling.. No differences for LTB4 or other lipid mediators were observed between diabetic and non-diabetic patients. RvD1 levels were below the threshold of quantification in most of the samples. A significant correlation was found between LTB4 and 5(S)-HETE levels. Omega 3 enrichment was not significantly different between control and diabetic plaques. There was a negative correlation between DHA/AA ratio and the level of 5(S)-HETE while there was a positive association with TXB2 and PGD2 concentrations.. Our results does not support the hypothesis of a specific involvement of LTB4 or COX-derived mediators in diabetic atherosclerosis. The relationship between DHA enrichment and the concentrations of specific inflammatory mediators within the plaque is of interest and will need to be confirmed in larger studies.

Topics: Atherosclerosis; Diabetes Mellitus, Type 2; Eicosanoids; Humans; Hydroxyeicosatetraenoic Acids; Leukotriene B4; Plaque, Atherosclerotic

The aim of the present study was to investigate the effect of genetic polymorphisms in candidate genes within the leukotriene (LT) pathway on platelet reactivity and the concentration of selected LTs in diabetic patients treated with acetylsalicylic acid (ASA). The study cohort consisted of 287 Caucasians with type 2 diabetes who had received treatment with ASA tablets (75 mg/day) for at least three months. Platelet reactivity analyses were performed using VerifyNow aspirin and PFA‑100 assays. The measured LTs included leukotriene B4 (LTB4) and leukotriene E4 (LTE4). Genotyping for the selected 25 single nucleotide polymorphisms (SNPs) within six genes of the LT pathway was performed using a Sequenom iPLEX platform. No statistically significant association was observed between the investigated SNP genotypes, platelet reactivity and measured LTs in the patient cohort. The results of our study suggest that certain polymorphisms of the LT pathway are not associated with altered platelet reactivity and the measured LTs in diabetic patients treated with ASA.

Topics: 5-Lipoxygenase-Activating Proteins; Aged; Alleles; Arachidonate 12-Lipoxygenase; Arachidonate 15-Lipoxygenase; Arachidonate 5-Lipoxygenase; Aspirin; Blood Platelets; Cohort Studies; Diabetes Mellitus, Type 2; Epoxide Hydrolases; Female; Gene Frequency; Genotype; Glutathione Transferase; Humans; Leukotriene B4; Leukotriene E4; Male; Middle Aged; Polymorphism, Single Nucleotide

In order to evaluate polymorphonuclear leukocyte (PMN) activity in diabetes mellitus, leukotriene B4 (LTB4) levels were measured in sixty patients, 31 affected with Type 1 diabetes mellitus and 29 affected with Type 2 diabetes mellitus. The LTB4 levels (12.1+/-0.2 pg/100 microl) in diabetic patients were higher compared to those of the control group (7.9+/-0.1 pg/100 microl) (P < 0.001), and remained significantly higher (P < 0.001) (12.8+/-0.2 pg/100 microl) than in the control group (11.0+/-0.2 pg/100 microl) after stimulation with calcium ionophore. A significant and positive correlation between glycated hemoglobin and LTB4 was demonstrated (P < 0.001, r = 0.80). This study demonstrates that in diabetic patients there is a PMN activation and that this activation is correlated to glycated hemoglobin level.

Topics: Adult; Aged; Blood Glucose; Calcimycin; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; In Vitro Techniques; Leukotriene B4; Male; Middle Aged; Neutrophils; Reference Values; Regression Analysis

In uterine tissue obtained from castrated control and non-insulin dependent diabetic (NIDDM) rats, eicosanoid production and its regulation by glucose levels and by the activity of phospholipase A2 (PLA2) was assessed. Basal outputs of prostaglandins (PGs) PGE2, PGE1, PGF2 alpha, 6-keto-PGF1 alpha (indicating the production of prostacyclin), thromboxane B2 (TXB2) (indicating the generation of TXA2) and leukotriene B4 (LTB4) were similar in control and NIDDM uterine preparations as assessed by RIA. When uterine conversion of labelled arachidonate into different prostanoids was evaluated, generation of 6-keto-PGF1 alpha, PGE2 and PGF2 alpha was similar in control and NIDDM uterine tissue, while TXB2 production was higher in the diabetic group. Moreover, when control tissue was incubated in the presence of elevated concentrations of glucose (22 mM) and compared to control tissue incubated in concentrations of glucose 11 mM, similar generation of 6-keto-PGF1 alpha, PGE2 and PGF2 alpha was observed, and higher concentrations of TXB2 were found, similar to those observed in diabetic uterine tissue. When NIDDM uterine tissue was incubated in the presence of glucose 22 mM, no difference in any prostanoid evaluated was observed when compared to values obtained in the presence of glucose 11 mM. In this work we have observed in NIDDM uterine tissue a normal TXA2 production when evaluated by RIA from endogenous arachidonic acid (AA) and a higher TXA2 generation from exogenous labelled AA. In addition PLA2 activity was found diminished in the NIDDM uteri in comparison to control uteri. A role of the diminished PLA2 as a protective mechanism that avoids TXA2 overproduction in uterine tissue from NIDDM rats is discussed.

Topics: 6-Ketoprostaglandin F1 alpha; Alprostadil; Animals; Arachidonic Acid; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Dinoprost; Dinoprostone; Eicosanoids; Female; Leukotriene B4; Ovariectomy; Phospholipases A; Phospholipases A2; Rats; Rats, Wistar; Thromboxane B2; Uterus