Titre du document / Document title

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

Auteur(s) / Author(s)

SANCHO Veronica ; NUCHE Bernardo ; ARNES Luis ; CANCELAS Jesus ; GONZALEZ Nieves ; DIAZ-MIGUEL Mariano ; MARTIN-DUCE Antonio ; VALVERDE Isabel ; VILLANUEVA-PENACARRILLO Maria L. ;

Résumé / 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.

Revue / Journal Title

International journal of molecular medicine   ISSN 1107-3756 

Source / Source

2007, vol. 19, n^o6, pp. 961-966 [6 page(s) (article)]

Langue / Language

Anglais

Editeur / Publisher

D.A. Spandidos, Athens, GRECE  (1998) (Revue)

Mots-clés d'auteur / Author Keywords

GLP-1 ; exendins ; glucose transport ; protein kinases ; adipocytes ; normal subjects ; morbidly obese patients ;

Localisation / Location

INIST-CNRS, Cote INIST : 27038, 35400014989918.0140