The action of GLP-1 and exendins upon glucose transport in normal human adipocytes, and on kinase activity as compared to morbidly obese patients

  • Authors:
    • Verónica Sancho
    • Bernardo Nuche
    • Luis Arnés
    • Jesús Cancelas
    • Nieves Gonz´lez
    • Mariano Díaz-Miguel
    • Antonio Martín-Duce
    • Isabel Valverde
    • María L. Villanueva-Peñacarrillo
  • View Affiliations

  • Published online on: June 1, 2007     https://doi.org/10.3892/ijmm.19.6.961
  • Pages: 961-966
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Abstract

A role of GLP-1 (glucagon-like peptide-1) in the recovery of the metabolic conditions of morbidly obese patients after bariatric surgery has been proposed. Exendin 4 (Ex-4) and exendin 9 (Ex-9) both have GLP-1-like effects upon glucose metabolism in human myocytes. We investigated in normal human adipocytes the effect of GLP-1, Ex-4 and Ex-9, compared with insulin upon the activity of PI3K, PKB, MAPKs and p70s6 kinases, and the participation of these enzymes in their action upon 2-deoxy-D-glucose transport by using potential inhibitors. The study was extended to morbidly obese patients. In normal subjects, GLP-1, Ex-4 and insulin, but not Ex-9, increased glucose uptake. In addition, GLP-1 and Ex-4 stimulated PI3K and MAPKs, similar to insulin, but not PKB. Ex-9 only enhanced PI3K, while none affected p70s6k. Inhibition of both PI3K and MAPKs blocked the stimulatory action of GLP-1, Ex-4 and insulin upon glucose transport. In obese patients, basal PI3K, PKB and MAPK activity was, as a rule, lower than that in normal subjects, while cells maintained their normal incremental response to GLP-1, Ex-4 or insulin; Ex-9 induced a clear stimulation of p42 MAPK. In summary, in normal human adipocytes, GLP-1 and Ex-4 have a protein kinase-dependent increasing effect upon glucose transport, which is impaired in obese patients. The participation of GLP-1 in the normalization of the metabolic conditions of the obese may occur through its effects on lipid metabolism or through effects upon glucose transport and/or metabolism in the liver and muscle, which in human obesity remain to be investigated.

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June 2007
Volume 19 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Sancho V, Nuche B, Arnés L, Cancelas J, Gonz´lez N, Díaz-Miguel M, Martín-Duce A, Valverde I and Villanueva-Peñacarrillo ML: The action of GLP-1 and exendins upon glucose transport in normal human adipocytes, and on kinase activity as compared to morbidly obese patients. Int J Mol Med 19: 961-966, 2007
APA
Sancho, V., Nuche, B., Arnés, L., Cancelas, J., Gonz´lez, N., Díaz-Miguel, M. ... Villanueva-Peñacarrillo, M.L. (2007). The action of GLP-1 and exendins upon glucose transport in normal human adipocytes, and on kinase activity as compared to morbidly obese patients. International Journal of Molecular Medicine, 19, 961-966. https://doi.org/10.3892/ijmm.19.6.961
MLA
Sancho, V., Nuche, B., Arnés, L., Cancelas, J., Gonz´lez, N., Díaz-Miguel, M., Martín-Duce, A., Valverde, I., Villanueva-Peñacarrillo, M. L."The action of GLP-1 and exendins upon glucose transport in normal human adipocytes, and on kinase activity as compared to morbidly obese patients". International Journal of Molecular Medicine 19.6 (2007): 961-966.
Chicago
Sancho, V., Nuche, B., Arnés, L., Cancelas, J., Gonz´lez, N., Díaz-Miguel, M., Martín-Duce, A., Valverde, I., Villanueva-Peñacarrillo, M. L."The action of GLP-1 and exendins upon glucose transport in normal human adipocytes, and on kinase activity as compared to morbidly obese patients". International Journal of Molecular Medicine 19, no. 6 (2007): 961-966. https://doi.org/10.3892/ijmm.19.6.961