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Nevertheless, the mechanisms governing this angiogenic paradox have not been elucidated. Xanthohumol (XN) and 8\u2010prenylnaringenin (8PN) beer polyphenols modulate angiogenesis, being thus targets for T2DM\u2010related complications. Our work examined whether polyphenols consumption affects angiogenic paradox and metabolism in a T2DM mouse model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>An increase in kidney and a reduction in left ventricle (LV) microvessels of diabetic C57Bl\/6 mice were observed. XN consumption reduced angiogenesis, VEGFR\u20102 expression\/activity, VEGF\u2010A and phosphofructokinase\u20102\/fructose\u20102,6\u2010bisphosphatase\u20103 enzyme expression, a metabolic marker present in endothelial tip cells in T2DM mice kidney. 8PN had opposite effects in T2DM mice LV. These XN and 8PN effects were dependent on VEGF levels as revealed by in vitro assays. These findings were accompanied by tissue and plasma reduced expression levels of VEGF\u2010B and its receptors, VEGFR1 and neuropilin\u20101, by both polyphenols.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Beer polyphenols modulate T2DM angiogenic paradox in a tissue\u2010dependent manner. We also show for the first time that both polyphenols decreased VEGF\u2010B pathway, which is implicated in endothelial\u2010to\u2010tissue lipid metabolism. Altogether, the effects of these polyphenols in the crosstalk between angiogenesis and metabolism render them potent agents for novel diabetic therapeutic interventions.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mnfr.201600488","type":"journal-article","created":{"date-parts":[[2016,12,6]],"date-time":"2016-12-06T05:22:46Z","timestamp":1481001766000},"source":"Crossref","is-referenced-by-count":20,"title":["Modulation of VEGF signaling in a mouse model of diabetes by xanthohumol and 8\u2010prenylnaringenin: Unveiling the angiogenic paradox and metabolism interplay"],"prefix":"10.1002","volume":"61","author":[{"given":"Raquel","family":"Costa","sequence":"first","affiliation":[{"name":"Department of Biochemistry Faculty of Medicine of the University of Porto  Porto Portugal"},{"name":"i3S, Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade Universidade do Porto  Porto Portugal"}]},{"given":"Ilda","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Faculty of Medicine of the University of Porto  Porto Portugal"}]},{"given":"Lu\u00edsa","family":"Guard\u00e3o","sequence":"additional","affiliation":[{"name":"Animal Facility Faculty of Medicine of the University of Porto  Porto Portugal"}]},{"given":"Joana Quelhas","family":"Lima","sequence":"additional","affiliation":[{"name":"Laboratory of Organic and Pharmaceutical Chemistry Department of Chemical Sciences FFUP \u2010 Faculty of Pharmacy University of Porto  Porto Portugal"}]},{"given":"Em\u00edlia","family":"Sousa","sequence":"additional","affiliation":[{"name":"Laboratory of Organic and Pharmaceutical Chemistry Department of Chemical Sciences FFUP \u2010 Faculty of Pharmacy University of Porto  Porto Portugal"},{"name":"CIIMAR\/CIMAR \u2013 Interdisciplinary Center of Marine and Environmental Research University of Porto  Porto Portugal"}]},{"given":"Raquel","family":"Soares","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Faculty of Medicine of the University of Porto  Porto Portugal"},{"name":"i3S, Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade Universidade do Porto  Porto Portugal"}]},{"given":"Rita","family":"Negr\u00e3o","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Faculty of Medicine of the University of Porto  Porto Portugal"},{"name":"i3S, Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade Universidade do Porto  Porto 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