Background: Green tea polyphenol (EGCG) has beneficial effects on cardiovascular dysfunction. Results: EGCG stimulates autophagy through a CaMKK␤-mediated mechanism, which contributes to degradation of lipid droplets. Conclusion: Regulation of autophagic flux by EGCG plays a role in intracellular lipid accumulation. Significance: Findings show a novel mechanism for beneficial effects of EGCG in cardiovascular complications.

. Activation of mTOR/p70S6 kinase by ANG II inhibits insulin-stimulated endothelial nitric oxide synthase and vasodilation. Am J Physiol Endocrinol Metab 302: E201-E208, 2012. First published October 25, 2011 doi:10.1152/ajpendo.00497.2011.-Elevated tissue levels of angiotensin II (ANG II) are associated with impairment of insulin actions in metabolic and cardiovascular tissues. ANG II-stimulated activation of mammalian target of rapamycin (mTOR)/p70 S6 kinase (p70S6K) in cardiovascular tissues is implicated in cardiac hypertrophy and vascular remodeling. However, the role of ANG II-stimulated mTOR/ p70S6K in vascular endothelium is poorly understood. In the present study, we observed that ANG II stimulated p70S6K in bovine aortic endothelial cells. ANG II increased phosphorylation of insulin receptor substrate-1 (IRS-1) at Ser 636/639 and inhibited the insulinstimulated phosphorylation of endothelial nitric oxide synthase (eNOS). An inhibitor of mTOR, rapamycin, attenuated the ANG II-stimulated phosphorylation of p70S6K and phosphorylation of IRS-1 (Ser 636/639 ) and blocked the ability of ANG II to impair insulin-stimulated phosphorylation of eNOS, nitric oxide production, and mesenteric-arteriole vasodilation. Moreover, point mutations of IRS-1 at Ser 636/639 to Ala prevented the ANG II-mediated inhibition of insulin signaling. From these results, we conclude that activation of mTOR/p70S6K by ANG II in vascular endothelium may contribute to impairment of insulin-stimulated vasodilation through phosphorylation of IRS-1 at Ser 636/639 . This ANG II-mediated impairment of vascular actions of insulin may help explain the role of ANG II as a link between insulin resistance and hypertension. angiotensin II; hypertension; insulin resistance; endothelial dysfunction; mammalian target of rapamycin; 70-kDa ribosomal S6 kinase; nitric oxide THE RENIN-ANGIOTENSIN SYSTEM (RAS) plays a crucial role in maintenance of vascular tone as well as other cardiovascular functions (3). Elevated levels of angiotensin II (ANG II) in the plasma and/or tissues contribute to various pathological conditions, including hypertension, coronary artery disease, and metabolic disorders, including insulin resistance and diabetes (14,17,26,48). ANG II is a potent vasoconstrictor that transmits signals through a G protein-coupled receptor, ANG II receptor 1 (AT1R) (40). Activation of AT1R is associated with impairment of insulin signaling, which may contribute to the pathophysiology of a number of cardiometabolic conditions, including hypertension, insulin resistance, and cardiomyopathy (41,49,51). However, the molecular mechanism for the AT1R-associated impairment of insulin signaling in vascular tissue is not completely understood.A number of the critical metabolic and vascular actions of insulin, including glucose uptake and nitric oxide (NO) production, occur through an insulin receptor (IR)/insulin receptor substrate-1 (IRS-1)/phosphoinositide 3-kinase (PI 3-kinase)/ protein kinase B (Akt) pathway (25,26,33). Insulin resistance in the vascul...

No abstract

Insulin resistance, a hallmark of metabolic disorders, is a risk factor for diabetes and cardiovascular disease. Impairment of insulin responsiveness in vascular endothelium contributes to insulin resistance. The reciprocal relationship between insulin resistance and endothelial dysfunction augments the pathophysiology of metabolism and cardiovascular functions. The most abundant green tea polyphenol, epigallocatechin-3-gallate (EGCG), has been shown to have vasodilator action in vessels by activation of endothelial nitric oxide synthase (eNOS). However, it is not known whether EGCG has a beneficial effect in high-fat diet (HFD)-induced endothelial dysfunction. Male C57BL/6J mice were fed either a normal chow diet (NCD) or HFD with or without EGCG supplement (50 mg·kg(-1)·day(-1)) for 10 wk. Mice fed a HFD with EGCG supplement gained less body weight and showed improved insulin sensitivity. In vehicle-treated HFD mice, endothelial function was impaired in response to insulin but not to acetylcholine, whereas the EGCG-treated HFD group showed improved insulin-stimulated vasodilation. Interestingly, EGCG intake reduced macrophage infiltration into aortic tissues in HFD mice. Treatment with EGCG restored the insulin-stimulated phosphorylation of eNOS, insulin receptor substrate-1 (IRS-1), and protein kinase B (Akt), which was inhibited by palmitate (200 μM, 5 h) in primary bovine aortic endothelial cells. From these results, we conclude that supplementation of EGCG improves glucose tolerance, insulin sensitivity, and endothelial function. The results suggest that EGCG may have beneficial health effects in glucose metabolism and endothelial function through modulating HFD-induced inflammatory response.

No abstract