Life sciences
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Monocyte chemotactic protein-1 (MCP-1) plays a pivotal role in the recruitment of monocytes and thus in the development of inflammatory cardiovascular diseases. Epigallocatechin-3-O-gallate (EGCG), the major catechin derived from green tea, has multiple beneficial effects to reduce cardiovascular disease but the effects of EGCG on vascular endothelial MCP-1 production is not known. In this study, we investigated the mechanisms by which EGCG may inhibit tumor necrosis factor-alpha (TNFalpha)-induced MCP-1 production in bovine coronary artery endothelial cells. ⋯ In conclusion, EGCG inhibited TNFalpha-induced MCP-1 production. Moreover, EGCG inhibited Akt phosphorylation as well as TNF activation of TNFR1, which subsequently resulted in reduced MCP-1 production. These data provide a novel mechanism where the green tea flavonoid, EGCG, could provide direct vascular benefits in inflammatory cardiovascular diseases.
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In the present study, we evaluated the autocrine modulatory effect of insulin on glucose metabolism and glucose-induced insulin secretion in islets isolated from hamsters with insulin resistance (IR) induced by administration of a sucrose-rich diet (SRD) during 5 weeks. We used an approach of two metabolic pathways (glucose oxidation and utilization) based on the measurement of 14CO2 and 3H2O production from D-[U-14C]-glucose and D-[5-(3)H]-glucose, respectively, in isolated islets incubated with 3.3 and 16.7 mM glucose alone, or with 5 or 15 mU/ml insulin, anti-insulin guinea-pig serum (1:500), 25 microM nifedipine, or 150 nM wortmannin. Insulin release was measured by radioimmunoassay in islets incubated with 3.3 or 16.7 mM glucose, with or without 75, 150, and 300 nM wortmannin. ⋯ Whereas wortmannin did not decrease insulin release induced by 16.7 mM glucose in SRD hamsters, it did in controls. We can conclude that the autocrine stimulatory effect of insulin upon glucose metabolism observed in normal islets is attenuated or even absent in islets from IR animals. Such decreased islet sensitivity to insulin did not prevent the compensatory secretion of insulin from maintaining glucose homeostasis, suggesting that, at least in this model, the islets can put forward alternative mechanisms to overcome such defect.