Characteristics of GLP-1 and exendins action upon glucose transport and metabolism in type 2 diabetic rat skeletal muscle

  • Authors:
    • Luis Arnés
    • Nieves González
    • Pilar Tornero-Esteban
    • Verónica Sancho
    • Alicia Acitores
    • Isabel Valverde
    • Elena Delgado
    • María L. Villanueva-Peñacarrillo
  • View Affiliations

  • Published online on: July 1, 2008     https://doi.org/10.3892/ijmm.22.1.127
  • Pages: 127-132
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Abstract

Exendin-4, a peptide 53% structurally homologous with glucagon-like peptide 1 (GLP-1), is insulinotropic and has an antidiabetic effect even more prolonged than that of GLP-1. Exendin-9 is an antagonist of GLP-1 receptor and action in several cell systems, but shows GLP-1- and exendin-4-agonistic characteristics in human muscle cells and tissue. The action of GLP-1 upon glucose transport and metabolism in muscle is mediated by specific receptors. In this study we investigated the effect of both exendin-4 and -9, relative to that of GLP-1, upon glucose transport and metabolism in the skeletal muscle from a streptozotocin-induced type 2 diabetic rat model, compared to normal. In normal rats, exendin-4, like GLP-1 and insulin, enhanced glucose uptake. This effect, which is mediated to a certain extent by some kinases (PI3K/ PKB, p70s6k and MAPKs), may be caused by the peptide acting, at least in part, through the muscle GLP-1 receptors. Exendin-9 also stimulated the same kinases, except for PKB, but failed to modify basal glucose uptake. Type 2 diabetic rats showed lower than normal basal muscle glucose transport and oxidation value, and higher glycogen synthase α activity and pyruvate release; however, no modification of glucose uptake by GLP-1 or exendin-4 was detected, at variance with insulin, and basal activity of PI3K/PKB was lower than normal, while that of p70s6k and MAPKs was higher. GLP-1 failed to affect the activity of any of the kinases, while exendin-4 increased the activity of PI3K, p70s6k and MAPKs, but not PKB, suggesting that this enzyme plays a major role in exendin-4 effect upon glucose transport in muscle.

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July 2008
Volume 22 Issue 1

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

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Spandidos Publications style
Arnés L, González N, Tornero-Esteban P, Sancho V, Acitores A, Valverde I, Delgado E and Villanueva-Peñacarrillo ML: Characteristics of GLP-1 and exendins action upon glucose transport and metabolism in type 2 diabetic rat skeletal muscle. Int J Mol Med 22: 127-132, 2008.
APA
Arnés, L., González, N., Tornero-Esteban, P., Sancho, V., Acitores, A., Valverde, I. ... Villanueva-Peñacarrillo, M.L. (2008). Characteristics of GLP-1 and exendins action upon glucose transport and metabolism in type 2 diabetic rat skeletal muscle. International Journal of Molecular Medicine, 22, 127-132. https://doi.org/10.3892/ijmm.22.1.127
MLA
Arnés, L., González, N., Tornero-Esteban, P., Sancho, V., Acitores, A., Valverde, I., Delgado, E., Villanueva-Peñacarrillo, M. L."Characteristics of GLP-1 and exendins action upon glucose transport and metabolism in type 2 diabetic rat skeletal muscle". International Journal of Molecular Medicine 22.1 (2008): 127-132.
Chicago
Arnés, L., González, N., Tornero-Esteban, P., Sancho, V., Acitores, A., Valverde, I., Delgado, E., Villanueva-Peñacarrillo, M. L."Characteristics of GLP-1 and exendins action upon glucose transport and metabolism in type 2 diabetic rat skeletal muscle". International Journal of Molecular Medicine 22, no. 1 (2008): 127-132. https://doi.org/10.3892/ijmm.22.1.127