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Int. J. Mol. Sci. 2017, 18(4), 750;

Delphinidin Reduces Glucose Uptake in Mice Jejunal Tissue and Human Intestinal Cells Lines through FFA1/GPR40

Institute of Pharmacology and Morphophysiology, Universidad Austral de Chile, 5110566 Valdivia, Chile
Centro de Estudios Científicos (CECs), Avenida Arturo Prat 514, 511046 Valdivia, Chile
Instituto de Biología y Genética Molecular (IBGM), Consejo Superior de Investigaciones Científicas (CSIC), 47003 Valladolid, Spain
Departamento de Bioquímica y Biología Molecular y Fisiología, Universidad de Valladolid, 47003 Valladolid, Spain
Author to whom correspondence should be addressed.
Academic Editors: Nuno Mateus and Iva Fernandes
Received: 21 February 2017 / Revised: 21 March 2017 / Accepted: 27 March 2017 / Published: 5 April 2017
(This article belongs to the Special Issue Anthocyanins)
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Anthocyanins are pigments with antihyperglycemic properties, and they are potential candidates for developing functional foods for the therapy or prevention of Diabetes mellitus type 2 (DM2). The mechanism of these beneficial effects of anthocyanins are, however, hard to explain, given their very low bioavailability due to poor intestinal absorption. We propose that free fatty acid receptor 1 (FFA1, also named GPR40), is involved in an inhibitory effect of the anthocyanidin delphinidin over intestinal glucose absorption. We show the direct effects of delphinidin on the intestine using jejunum samples from RF/J mice, and the human intestinal cell lines HT-29, Caco-2, and NCM460. By the use of specific pharmacological antagonists, we determined that delphinidin inhibits glucose absorption in both mouse jejunum and a human enterocytic cell line in a FFA1-dependent manner. Delphinidin also affects the function of sodium-glucose cotransporter 1 (SGLT1). Intracellular signaling after FFA1 activation involved cAMP increase and cytosolic Ca2+ oscillations originated from intracellular Ca2+ stores and were followed by store-operated Ca2+ entry. Taken together, our results suggest a new GPR-40 mediated local mechanism of action for delphinidin over intestinal cells that may in part explain its antidiabetic effect. These findings are promising for the search for new prevention and pharmacological treatment strategies for DM2 management. View Full-Text
Keywords: delphinidin; anthocyanins; SGLT1; glucose; GPR40; FFA1 delphinidin; anthocyanins; SGLT1; glucose; GPR40; FFA1

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Hidalgo, J.; Teuber, S.; Morera, F.J.; Ojeda, C.; Flores, C.A.; Hidalgo, M.A.; Núñez, L.; Villalobos, C.; Burgos, R.A. Delphinidin Reduces Glucose Uptake in Mice Jejunal Tissue and Human Intestinal Cells Lines through FFA1/GPR40. Int. J. Mol. Sci. 2017, 18, 750.

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