Low phospholipid arachidonic acid values in diabetic platelets.

Jones, David B.; Carter, R D; Haitas, B; Mann, J I

doi:10.1136/bmj.286.6360.173

Cited by 88 publications

(37 citation statements)

References 17 publications

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“…The first step in the synthesis of prostaglandins in the platelet is the liberation of arachidonic acid from the platelet membrane by the action of phospholipase Aj. Increased activity of this enzyme in diabetics, as shown by Takeda et al [1981] corresponds well with the low ara chidonic acid levels found in diabetic plate- lets by Jones et al [1983]. Normal platelet function is related to cyclic AMP levels in the platelet.…”

Section: Prostaglandin Metabolismsupporting

confidence: 53%

Factors of the Hemostatic System in Diabetic Patients

Ostermann¹,

Loo²

1986

Pathophysiol Haemos Thromb

104

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Diabetes mellitus is associated with a variety of vascular complications like diabetic retinopathy, myocardial infarction, stroke and peripheral vessel disease. These complications are of utmost importance because they lead to disability and premature death of the patients. The pathogenesis of these lesions has been thought to depend at least partly on defects in the hemostatic system. Many alterations of the coagulation and the fibrinolytic system as well as of the reaction of platelets have been found in diabetics. In general these tend to suggest a state of slightly activated coagulation, of increased platelet reactivity and of decreased fibrinolysis. However, no conclusive picture of the role of hemostasis in the development of vascular lesions in diabetics has emerged yet, as contradictive results have been found by many investigators. The aim of this review article is to sum up the knowledge that has accumulated in the last years in controlled clinical trials concerning the state of the diabetic hemostatic system.

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Section: Prostaglandin Metabolismsupporting

confidence: 53%

Factors of the Hemostatic System in Diabetic Patients

Ostermann¹,

Loo²

1986

Pathophysiol Haemos Thromb

104

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“…Therefore, increased arachidonic acid content in diabetic platelet phospholipids [3,4] was considered as one possible cause of increased TXA2 synthesis in diabetic platelets [12][13][14]. However, Jones et al [15] recently reported a significant decrease in arachidonic acid levels in diabetic platelet phospholipids, a result quite different from ours. It has been demonstrated that the synthesis of prostaglandin precursors, polyunsaturated fatty acids, is influenced by insulin [16] and ageing [17].…”

Section: Discussioncontrasting

confidence: 53%

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

et al. 1984

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Summary. Arachidonic acid uptake activity was measured in platelets obtained from 27 Type 2 diabetic patients and 18 agematched control subjects. In both groups after 1 h incubation almost all the incorporated 14C-arachidonic acid was located in the phospholipids of the platelets. Arachidonic acid was predominantly incorporated into phosphatidylcholine. The radioactivity incorporated into platelets increased linearly with incubation time, up to 90 min. The linear increase was observed at arachidonic acid concentrations of 0.1-1.0 ~tg/ml in both groups. The rate of incorporation of radioactivity in diabetic platelets was about 1.4 times higher than that in control platelets at all arachidonic acid concentrations studied. The arachidonic acid uptake activity of diabetic platelets (577 + 26 ng/60 min per 109platelets) was significantly higher than that in control platelets (410_ 26 ng/60 rain per 109plate -lets).No significant correlations were found between the arachidonic acid uptake activity and fasting plasma glucose, total cholesterol or triglyceride levels. The arachidonic acid uptake activity of platelets was significantly higher in diabetic patients with proliferative retinopathy than in those with little or no background retinopathy. In addition, there were no significant differences between control and diabetic subjects in the uptake activity of platelets for linoleic acid and oleic acid. These data may explain the elevated arachidonic acid content in diabetic platelet phospholipids and enhancement of thromboxane synthesis in diabetes.Key words: Arachidonic acid uptake, platelet phospholipids, Type 2 diabetes, retinopathy, platelet-rich plasma, non-esterifled fatty acid.Thromboxane A2 (TXA2), biosynthesized from arachidonic acid in platelet phospholipids, plays an important rrle in the process of platelet aggregation [1,2]. It is postulated that the balance between platelet TXA2 and vascular prostacyclin production might be a crucial step in the development of atherosclerosis and arterial thrombosis in diabetes mellitus. Recently, Kalofoutis and Lekakis [3] and we [4] have demonstrated that the arachidonic acid content of platelet phospholipids was increased in diabetes. It is generally accepted that the TXA2 synthesis rate is regulated at the step of liberation of arachidonic acid from membrane phospholipids [5]. Therefore, increased esterified arachidonic acid content in phospholipids might modulate TXA2 production in diabetes.In this study, we examined the t4C-arachidonic acid uptake activity of platelets obtained from Type 2 (noninsulin-dependent) diabetic patients and age-matched control subjects, to clarify the mechanisms of increased arachidonic acid levels in platelet phospholipids in diabetes. Subjects and methods SubjectsThe Type 2 diabetic subjects included in the study were t0 men and 17 women ranging in age between 48 and 86 years (mean 67 + 2 years). Eleven patients were treated with insulin and 16 were treated with sulphonylureas. The control subjects (five men and 13 women, age range 46-79...

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“…Further studies are needed to elucidate the degree to which alterations in prostanoid metabolism of diabetic patients [12][13][14][15][16][17][18][19][20] are based on disturbances in the synthesis of the precursor PUFA.…”

Section: Discussionmentioning

confidence: 99%

“…In fact, several abnormalities of the platelet function and prostaglandin metabolism have been described in human diabetes [12][13][14][15]. Cross-sectional studies have shown that ARA-content of diabetic platelets may be increased [17,18], normal [19] or decreased [20], the latter especially in cases with severe retinopathy [201. We have recently observed that in women with Type 1 diabetes the content of linoleic acid of serum lipids was higher and that of ARA and other n-6 PUFA lower than in controls [3].…”

mentioning

confidence: 99%

Improvement of diabetic control by continuous subcutaneous insulin infusion therapy changes fatty acid composition of serum lipids and erythrocytes in Type 1 (insulin-dependent) diabetes

1986

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Summary. The influence of improved diabetic control on the fatty composition of serum lipids, erythrocytes and platelets was investigated in 24patients with Type 1 (insulin-dependent) diabetes treated for 6 months with either continuous subcutaneous insulin infusion (n = 14) or conventional insulin therapy (n = 10). The groups were matched for age, sex, body mass index, serum lipids, duration of diabetes, glycosylated haemoglobin and insulin dose. Glycaemic control improved, and the contents of dihomogammalinolenic acid and arachidonic acid but not linoleic acid rose significantly (p < 0.05), in serum lipids of patients treated with continuous infusion. No changes were observed in the group treated with insulin injections. Both in serum and erythrocytes the n-6 polyunsaturated fatty acid ratios rose consistently in the patients, with improvement of control regardless of the mode of treatment. Furthermore, the change of HbA1 was negatively correlated with that of arachidonic acid in erythrocytes. No changes were found in the platelet fatty acid compositions. The findings suggest that improved diabetic control enhances the conversion of linoleic acid to arachidonic acid, probably by activating enzymes needed for chain elongation and desaturation.

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Low phospholipid arachidonic acid values in diabetic platelets.

Cited by 88 publications

References 17 publications

Factors of the Hemostatic System in Diabetic Patients

Factors of the Hemostatic System in Diabetic Patients

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

Improvement of diabetic control by continuous subcutaneous insulin infusion therapy changes fatty acid composition of serum lipids and erythrocytes in Type 1 (insulin-dependent) diabetes

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