Myricetin, quercetin and catechin-gallate inhibit glucose uptake in isolated rat adipocytes

Pablo Strobel, Claudio Allard, Tomás Perez-Acle, Rosario Calderon, Rebeca Aldunate, Federico Leighton

Resultado de la investigación: Contribución a una revistaArtículo

180 Citas (Scopus)

Resumen

The facilitative glucose transporter, GLUT4, mediates insulin-stimulated glucose uptake in adipocytes and muscles, and the participation of GLUT4 in the pathogenesis of various clinical conditions associated with obesity, visceral fat accumulation and insulin resistance has been proposed. Glucose uptake by some members of the GLUT family, mainly GLUT1, is inhibited by flavonoids, the natural polyphenols present in fruits, vegetables and wine. Therefore it is of interest to establish if these polyphenolic compounds present in the diet, known to be effective antioxidants but also endowed with several other biological activities such as protein-tyrosine kinase inhibition, interfere with GLUT4 function. In the present study, we show that three flavonoids, quercetin, myricetin and catechin-gallate, inhibit the uptake of methylglucose by adipocytes over the concentration range of 10-100 μM. These three flavonoids show a competitive pattern of inhibition, with Ki = 16, 33.5 and 90 μM respectively. In contrast, neither catechin nor gallic acid inhibit methylglucose uptake. To obtain a better understanding of the interaction among GLUT4 and flavonoids, we have derived a GLUT4 three-dimensional molecular comparative model, using structural co-ordinates from a GLUT3 comparative model and a mechanosensitive ion channel [PDB (Protein Data Bank) code 1MSL] solved by X-ray diffraction. On the whole, the experimental evidence and computer simulation data favour a transport inhibition mechanism in which flavonoids and GLUT4 interact directly, rather than by a mechanism related to protein-tyrosine kinase and insulin signalling inhibition. Furthermore, the results suggest that GLUT transporters are involved in flavonoid incorporation into cells.

Idioma originalInglés
Páginas (desde-hasta)471-478
Número de páginas8
PublicaciónBiochemical Journal
Volumen386
N.º3
DOI
EstadoPublicada - 15 mar 2005

Áreas temáticas de ASJC Scopus

  • Bioquímica
  • Biología celular
  • Biología molecular

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    Strobel, P., Allard, C., Perez-Acle, T., Calderon, R., Aldunate, R., & Leighton, F. (2005). Myricetin, quercetin and catechin-gallate inhibit glucose uptake in isolated rat adipocytes. Biochemical Journal, 386(3), 471-478. https://doi.org/10.1042/BJ20040703