PPARγ-dependent and -independent effects of Rosiglitazone on lipotoxic human pancreatic islets - Inserm - Institut national de la santé et de la recherche médicale Accéder directement au contenu
Article Dans Une Revue Biochemical and Biophysical Research Communications Année : 2008

PPARγ-dependent and -independent effects of Rosiglitazone on lipotoxic human pancreatic islets

Résumé

We explored the in vitro effects of Rosiglitazone (RZG), a PPARgamma agonist, on human pancreatic islet dysfunctions induced by chronic free fatty acid exposure. We demonstrated that RZG beneficial effects on insulin secretion and apoptosis did not imply PDX-1 or insulin gene modulation. It rather involved, through a PPARgamma-dependent mechanism, a reduction of iNOS overexpressed in lipotoxic islets. This reduction likely led to the restoration of ATP level and insulin secretion as well as the decrease in apoptosis. More interestingly, we also demonstrated that RZG beneficial effects involved PPARgamma-independent mechanisms. RZG treatment led to a limitation of oxidative stress exemplified by an increase of GPx and SOD expression. It also increased UCP2 expression that seemed to display antioxidant action in this model. Thus, RZG did not appear to exert a direct action on insulin expression but rather an indirect action on insulin secretion and apoptosis, through PPARgamma-dependent and -independent mechanisms, via regulation of nitrogen and oxygen reactive species injury.

Dates et versions

inserm-04532358 , version 1 (04-04-2024)

Identifiants

Citer

Brigitte Vandewalle, Ericka Moerman, Bruno Lefebvre, Frédérique Defrance, Valéry Gmyr, et al.. PPARγ-dependent and -independent effects of Rosiglitazone on lipotoxic human pancreatic islets. Biochemical and Biophysical Research Communications, 2008, 366 (4), pp.1096-1101. ⟨10.1016/j.bbrc.2007.12.088⟩. ⟨inserm-04532358⟩

Collections

INSERM UNIV-LILLE
3 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More