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: Article

176 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 originalEnglish
Páginas (desde-hasta)471-478
Número de páginas8
PublicaciónBiochemical Journal
Volumen386
N.º3
DOI
EstadoPublished - 15 mar 2005

Huella dactilar

Quercetin
Flavonoids
Adipocytes
Rats
Glucose
Insulin
Protein-Tyrosine Kinases
Polyphenolic compounds
Gallic Acid
Molecular Models
Wine
Intra-Abdominal Fat
Facilitative Glucose Transport Proteins
Catechin
Vegetables
Polyphenols
Nutrition
Fruits
Bioactivity
Ion Channels

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Citar esto

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
Strobel, Pablo ; Allard, Claudio ; Perez-Acle, Tomás ; Calderon, Rosario ; Aldunate, Rebeca ; Leighton, Federico. / Myricetin, quercetin and catechin-gallate inhibit glucose uptake in isolated rat adipocytes. En: Biochemical Journal. 2005 ; Vol. 386, N.º 3. pp. 471-478.
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abstract = "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.",
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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, vol. 386, n.º 3, pp. 471-478. https://doi.org/10.1042/BJ20040703

Myricetin, quercetin and catechin-gallate inhibit glucose uptake in isolated rat adipocytes. / Strobel, Pablo; Allard, Claudio; Perez-Acle, Tomás; Calderon, Rosario; Aldunate, Rebeca; Leighton, Federico.

En: Biochemical Journal, Vol. 386, N.º 3, 15.03.2005, p. 471-478.

Resultado de la investigación: Article

TY - JOUR

T1 - Myricetin, quercetin and catechin-gallate inhibit glucose uptake in isolated rat adipocytes

AU - Strobel, Pablo

AU - Allard, Claudio

AU - Perez-Acle, Tomás

AU - Calderon, Rosario

AU - Aldunate, Rebeca

AU - Leighton, Federico

PY - 2005/3/15

Y1 - 2005/3/15

N2 - 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.

AB - 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.

KW - Catechin-gallate

KW - Flavonoid

KW - Glucose transporter

KW - Molecular dynamics

KW - Myricetin

KW - Quercetin

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Strobel P, Allard C, Perez-Acle T, Calderon R, Aldunate R, Leighton F. Myricetin, quercetin and catechin-gallate inhibit glucose uptake in isolated rat adipocytes. Biochemical Journal. 2005 mar 15;386(3):471-478. https://doi.org/10.1042/BJ20040703