Repository of Research and Investigative Information

Repository of Research and Investigative Information

Ilam University of Medical Sciences

Rosiglitazone, a PPAR gamma agonist, ameliorates palmitate-induced insulin resistance and apoptosis in skeletal muscle cells

Sun Oct 2 23:52:34 2022

(2014) Rosiglitazone, a PPAR gamma agonist, ameliorates palmitate-induced insulin resistance and apoptosis in skeletal muscle cells. Cell Biochemistry and Function. pp. 683-691. ISSN 0263-6484

Full text not available from this repository.

Official URL: http://apps.webofknowledge.com/InboundService.do?F...

Abstract

Palmitate induces insulin resistance and apoptosis in insulin target tissues. Rosiglitazone (RSG), a peroxisome proliferator-activated receptor (PPAR) agonist, can activate both pro-apoptotic and anti-apoptotic pathways in different cells; however, its effect on palmitate-induced apoptosis in skeletal muscle cells remains to be elucidated. After differentiation of C2C12 cells, myotubes were treated with palmitate, RSG and GW9662 (PPAR antagonist). MTT and terminal deoxynucleotide transferase dUTP nick end labelling (TUNEL) assays and caspase-3 activity were used to investigate the apoptosis. To study the underlying mechanism, glucose uptake, gene expression and protein levels were evaluated. A total of 0.75mM palmitate reduced cell viability by 43 and increased TUNEL-positive cells and caspase-3 activity by 15-fold and 6.6-fold, respectively. RSG (10M) could markedly decrease the level of TUNEL-positive cells and caspase-3 activity in palmitate-treated cells. The protective effect of RSG on apoptosis was abrogated by GW9662. To investigate the molecular mechanism of this effect, gene expression and protein level of protein tyrosine phosphatase 1B (PTP1B) were evaluated. Palmitate and RSG individually increased the expression and protein level of PTP1B, whereas combined treatment (palmitate and RSG) were able to further increase the expression of PTP1B in C2C12 cells. We also evaluated the effect of RSG on palmitate-induced insulin resistance in muscle cells. RSG could significantly improve glucose uptake by 0.4-fold in myotubes treated with palmitate. Moreover, RSG could restore the phosphorylation of Akt in palmitate-treated cells. These data suggest that RSG protects skeletal muscle cells against palmitate-induced apoptosis and this effect appears to be mediated via the PPAR-dependent and PTP1B-independent mechanisms. Copyright (c) 2014 John Wiley & Sons, Ltd. SIGNIFICANCE OF THE STUDYSaturated free fatty acids (FFAs), such as palmitate, have been shown to induce cellular apoptosis. Strategies for preventing the cytotoxic effect of palmitate are useful in reduction of diabetes complications. In this study, we introduced RSG as an agent that protects skeletal muscle cells against palmitate-induced apoptosis and insulin resistance. It appears that RSG protects skeletal muscle cells against palmitate-induced apoptosis via the PPAR-dependent and PTP1B-independent mechanisms. Given the role of FFAs in skeletal muscle apoptosis, these findings support the idea that RSG can ameliorate diabetes complications such as skeletal muscle loss.

Item Type: Article
Creators:
CreatorsEmail
Meshkani, R.UNSPECIFIED
Sadeghi, A.UNSPECIFIED
Taheripak, G.UNSPECIFIED
Zarghooni, M.UNSPECIFIED
Gerayesh-Nejad, S.UNSPECIFIED
Bakhtiyari, S.UNSPECIFIED
Keywords: rosiglitazone palmitate skeletal muscle cells PTP1B C2C12 apoptosis tyrosine-phosphatase 1b activated-receptor-gamma endoplasmic-reticulum stress pancreatic beta-cells saturated fatty-acids oxidative stress mitochondrial dysfunction ceramide content c2c12 myotubes thiazolidinediones Biochemistry & Molecular Biology Cell Biology
Divisions:
Page Range: pp. 683-691
Journal or Publication Title: Cell Biochemistry and Function
Journal Index: ISI
Volume: 32
Number: 8
Identification Number: https://doi.org/10.1002/cbf.3072
ISSN: 0263-6484
Depositing User: مهندس مهدی شریفی
URI: http://eprints.medilam.ac.ir/id/eprint/626

Actions (login required)

View Item View Item