Increased arachidonic acid incorporation into platelet phospholipids in Type 2 (non-insulin-dependent) diabetes

Takahashi, Ryutaro; Morita, Ikuo; Saito, Yumiko; Ito, Hideki; Murota, Sei‐itsu

doi:10.1007/bf00281120

Cited by 34 publications

(10 citation statements)

References 19 publications

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“…Some studies have shown lower levels of linoleic acid and higher levels of the more highly unsaturated linoleic acid metabolites, one being arachidonic acid [15,16]. Other studies have shown the plasma linoleic acid levels from diabetic patients to be similar to control subjects but with different levels of linoleic acid metabolites [17][18][19]. Peterson et al [20] have recently shown higher proportions of linoleic acid and lower proportions of arachidonic acid and oleic acid in erythrocytes and plasma triglycerides isolated from Asian diabetic subjects compared with European diabetic subjects.…”

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confidence: 99%

Oxidation of low-density lipoprotein in NIDDM: its relationship to fatty acid composition

et al. 1995

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Summary The increased risk of atherosclerotic disease in diabetic subjects may be due to enhanced foam cell formation following an increased susceptibility of low density lipoprotein to oxidative modification. This study has compared fatty acid content and lipoprotein oxidisability in 10 non-insulin-dependent diabetic subjects with that in 10 control subjects. Both groups were normocholesterolaemic and the diabetic subjects had higher triglyceride levels (2.2 + 0.4 vs 1.2 + 0.2 mmol/1, p < 0.05). The fatty acid composition was compared in low density lipoprotein following Folch extraction, separation by thin layer chromatography (for the lipid classes) and analysis by gas liquid chromatography. Low density lipoprotein oxidisability was assessed by conjugated diene and thiobarbituric acid reacting substance formation in the presence of copper ions. The esterified/free cholesterol ratio was higher in the low density lipoprotein from patients compared to control subjects (2.9 _+ 0.1 vs 1.9 + 0.3, p < 0.05). Linoleic acid in the cholesteryl ester fraction of the lipoprotein was higher in the patients than in the control subjects (48.2 + 2.2 % vs 42.4 + 3.4 %,p < 0.05) as was the total quantity of linoleic acid in the cholesteryl ester fraction (317.8 + 68.0 vs 213.2 + 28.0 vg/mg protein, p < 0.05) and in the low-density lipoprotein as a whole (443.2 + 70.0 vs 340.2 + 28.2 ~g/mg protein, p<0.05). Lipoprotein oxidisability was also increased in the diabetic group with increased formation of thiobarbituric acid reacting substances (35.6 + 7.2 vs 22.3 + 3.5 nmol/mg protein, p < 0.05, increased total diene formation (502 + 60 vs 400 + 30 nmol/mg protein, p < 0.05) and increased rate of diene formation (7.2 + 0.6 vs 5.1 + 0.9 nmol diene 9 mg protein -1. min -1, p < 0.05). This study indicates that low-density lipoprotein from diabetic subjects is more susceptible to oxidation. This could, in vivo, accelerate foam-cell formation thereby increasing atherosclerotic risk in diabetic subjects. [Diabetologia (1995[Diabetologia ( ) 38: 1300[Diabetologia ( -1306 Key words Non-insulin-dependent diabetes mellitus, low-density lipoprotein oxidation, dietary fatty acids, low-density lipoprotein composition, glycated lowdensity lipoprotein.Although hypercholesterolaemia is an important risk factor in both diabetic and non-diabetic subjects, lowdensity lipoprotein (LDL) cholesterol levels are of- ten normal in patients with atherosclerosis. In this study attention has been focused on abnormalities in the composition of LDL the major cholesterol-carrying particle, rather than the quantity. These investigations have been prompted by the finding that oxidised rather than native LDL delivers cholesterol to the macrophage [1], the precursor of the foam cell and the maj or cholesterol-containing cell in the atherosclerotic plaque. Therefore, the potential for LDL to be oxidised in the vessel wall may be of importance in atherogenesis. Babiy et al. [2] have shown that LDL from non-insulin-dependent diabetic (NIDDM)

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confidence: 99%

Oxidation of low-density lipoprotein in NIDDM: its relationship to fatty acid composition

et al. 1995

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“…Several studies have been conducted to investigate the mechanism(s) responsible for the enhanced platelet responsiveness to aggregation and release-induced stimuli in both man and animals with diabetes [9,10]. Most of these studies have focused on whether the arachidonic acid metabolism of platelets is altered in diabetes [11,12,24]. Recently, the breakdown of phosphoinositides has drawn attention as being the earliest even underlying the reactivity ofplatelets.…”

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confidence: 99%

“…Moreover, enhanced arachidonic acid release and thromboxane production have been reported in platelets from NIDDM patients [11,12]. Recently there have been reports [13][14][15] focusing on thrombin-induced changes in phosphoinositide metabolism in diabetic patients.…”

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confidence: 99%

Thrombin-induced platelet aggregation, phosphoinositide metabolism and protein phosphorylation in NIDDM patients treated by diet, sulphonylurea or insulin

et al. 1994

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SummaryWe studied thrombin-induced metabolism of phosphoinositide, protein phosphorylation and platelet aggregation in platelets from 32 NIDDM patients and 12 control subjects. To clarify the effect of diet, sulphonylureas, or insulin treatment, the subjects were divided into three groups based on the type of treatment. Thrombin-induced platelet aggregation was measured with an aggregometer. Low-dose thrombin (0.25 U/ml)-stimulated platelet aggregation in diabetic patients was significantly increased compared with the control subjects. Platelet aggregation in the sulphonylurea and insulin groups was significantly lower than in the diet group. On the other hand, in platelets incubated with p2p]orthophosphate, thrombin-induced incorporation of 32p radioactivity into phosphatidic acid (PA) was significantly lower in the sulphonylurea and insulin groups than in the diet group. Thrombin-induced incorporation of [32p] radioactivity into phosphatidylinositol (PIP) for 10 s was significantly higher in the sulphonylurea group than in the diet group. There were no differences in thrombin-induced 47kDa protein phosphorylation between platelets from the diet, sulphonylurea, or insulin groups. These results suggest that sulphonylureas and insulin induce suppression of thrombin-induced activation of phospholipase C, which mediates hydrolysis of PIP and PIP2 and production of PA, which leads to inhibition of platelet aggregation. [Diabetologia (1994) 37: 632-638[

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“…To assess changes in AA metabolism, the incorporation of [ 3 H]AA into platelet membrane phospholipids [19], predominantly into phosphatidylcholine [20], was evaluated. Platelets were labeled with 0.5 ÌCi/ml [ 3 H]AA for 30 min at 37°C in phosphate buffer (pH 6.5).…”

Section: Methodsmentioning

confidence: 99%

Nitric Oxide Production and Arachidonic Acid Metabolism in Platelet Membranes of Coronary Heart Disease Patients with and without Diabetes

Tretjakovs

Kalnins²,

Dabina³

et al. 2003

Med Princ Pract

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Aim: To evaluate the levels of nitrite (NO^–₂) and nitrate (NO^–₃) ions and the incorporation of [³H]arachidonic acid (AA) into phospholipids of platelet membranes from coronary artery disease (CAD) patients with and without diabetes (NIDDM). Subjects and Methods: Eighteen CAD patients (group A), 18 CAD patients with NIDDM (group B), and 20 healthy controls (group C) without dyslipidemia, peripheral vascular disease and hypertension were included in the study. The groups were matched for age, sex and body mass index. The diagnosis of CAD was confirmed by coronary angiography. The nitric oxide end products (NOx), NO^–₂ plus NO^–₃ ions in platelet membranes, were determined using a spectrophotometric method based on the Griess reaction. The turnover of phospholipids was evaluated by incorporation of [³H]AA into platelet membrane phospholipids. Results: A significantly smaller amount of NOx ions was in the platelet membrane of groups A (40 ± 8 µmol/l) and B (29 ± 10 µmol/l) than C (57 ± 6 µmol/l), p < 0.001. Conversely a significantly greater amount of [³H]AA was incorporated into platelet phospholipids of group B patients (5,123 ± 1,637 dpm/mg) than groups A (3,159 ± 1,253 dpm/mg; p < 0.002) and C (1,621 ± 417 dpm/mg). An inverse correlation between [³H]AA incorporation and NOx levels was established: r = –0.76 (p < 0.05, n = 36) in CAD patients. Conclusions: Diabetes in CAD patients decreased the ability to produce platelet-derived NO and affects AA metabolism. This may result in higher platelet sensitivity to aggregating stimuli.

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Increased arachidonic acid incorporation into platelet phospholipids in Type 2 (non-insulin-dependent) diabetes

Cited by 34 publications

References 19 publications

Oxidation of low-density lipoprotein in NIDDM: its relationship to fatty acid composition

Oxidation of low-density lipoprotein in NIDDM: its relationship to fatty acid composition

Thrombin-induced platelet aggregation, phosphoinositide metabolism and protein phosphorylation in NIDDM patients treated by diet, sulphonylurea or insulin

Nitric Oxide Production and Arachidonic Acid Metabolism in Platelet Membranes of Coronary Heart Disease Patients with and without Diabetes

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