Elevated glucose alters eicosanoid release from porcine aortic endothelial cells.

Abstract

Cultured porcine aortic endothelial cells were conditioned through two passages to mimic euglycemic and hyperglycemic conditions (5.2 mM, normal glucose; 15.6 mM, elevated glucose). After incubation with 1 ,uM I'4Clarachidonic acid for 24 h, the cells were stimulated with 1 ,uM A23187 for times up to 30 min. Uptake of ['4Clarachidonic acid and its distribution among cell lipids were unaffected by the increased glucose concentration. The release of eicosanoids from labeled cells and unlabeled cells was measured by reverse-phase HPLC and by RIA, respectively. Compared with cells stimulated in the presence of normal glucose concentrations, cells stimulated in the presence of elevated glucose released 62.6% less free 114q-arachidonic acid, but released 129% more 14C-labeled 15-hydroxyeicosatetraenoic acid (HETE). Increased release of 15-HETE in the presence of elevated glucose in response to A23187, bradykinin, and thrombin was confirmed by RIA. A similar increase in 5-HETE release was observed by RIA after A23187 treatment. The release of both radiolabeled and unlabeled prostanoids was equal at both glucose concentrations. The data indicate that glucose may play an important role in the regulation of release and metabolism of arachidonic acid after agonist stimulation. In the presence of elevated glucose concentrations, such as those associated with diabetes mellitus, the extent and pattern of eicosanoid release from endothelial cells is markedly altered.

Early onset of subclinical atherosclerosis in women with gestational diabetes mellitus

“…Free radicals inactivate endothelium-derived nitric oxide 27,28 , interfere with endothelial-dependent vasodilatation 27 and are produced during prostaglandin formation 29,30 . Increased prostaglandin synthesis has been demonstrated in models of both acute and chronic hyperglycemia 31,32 . Alternatively, hyperglycemia may lead directly to the formation of free radicals by glucose auto-oxidation 33 .…”

Vitamin C improves endothelium-dependent vasodilation in patients with non-insulin-dependent diabetes mellitus.

“…Autoxidation of glucose catalyzed by transition metals and glycosylation of proteins can also generate excess oxygen-derived free radicals (55)(56)(57). Lastly, experimental hyperglycemia in animals increases AA metabolism and eicosanoid synthesis (33,37,58,59). Enhanced eicosanoid synthesis results in increased production of oxygen-derived free radicals (60)(61)(62).…”

Hyperglycaemia modifies the reaction of microvessels to insulin in rat skeletal muscle

“…The haemodynamic effects of osmolality are largely unknown but, if anything, are rather characterized by vasodilation [34,35]. Second, a direct constrictive effect of glucose could also result from enhanced production of some prostanoïds [36,37], endothelin [38] or a stimulation of protein kinase C [39--41]. Third, since vessel caliber is also largely influenced by metabolites in the surrounding tissue, products of local glucose utilization in the muscle may have induced local vasoconstriction.…”