, Volume 44, Issue 1, pp 87–98

Rosiglitazone protects against palmitate-induced pancreatic beta-cell death by activation of autophagy via 5′-AMP-activated protein kinase modulation


  • Jie Wu
    • Department of Endocrinology, Chang Hai HospitalThe Second Military Medical University
    • Department of Endocrinology, Tong Ji HospitalTong Ji University
  • Jun-jie Wu
    • National Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life SciencesFudan University
  • Lin-jun Yang
    • Department of Oncology, Chang Hai HospitalThe Second Military Medical University
  • Li-xin Wei
    • Department of Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery HospitalThe Second Military Medical University
    • Department of Endocrinology, Chang Hai HospitalThe Second Military Medical University
Original Article

DOI: 10.1007/s12020-012-9826-5

Cite this article as:
Wu, J., Wu, J., Yang, L. et al. Endocrine (2013) 44: 87. doi:10.1007/s12020-012-9826-5


Promoting beta-cell survival is crucial for the prevention of beta-cell failure in diabetes. Thiazolidinediones, a widely used drug to improve insulin sensitivity in clinical practice, is found to have a protective effect on islet beta-cell. To date, the mechanism underlying the protective role of thiazolidinedione on beta-cell survival remain largely unknown. Activation of autophagy was detected by transmission electron microscopy, western blot, and GFP-LC3 transfection. Cell viability was examined by WST-8. Cell apoptosis was demonstrated by DAPI and Annexin V/PI staining. Colony formation assay was used to detect long-term cell viability. We demonstrated that rosiglitazone-treated beta-cells were more resistant to palmitate-induced apoptosis. The conversion of LC3-I to LC3-II and accumulated autophagosomes were found to be upregulated in rosiglitazone-treated cells. Inhibition of autophagy augmented palmitate-induced apoptosis with rosiglitazone treatment, suggesting that autophagy plays an important role in the survival function of rosiglitazone on beta-cells. Furthermore, we showed that rosiglitazone could induce AMP-activated protein kinase (AMPK) phosphorylation and reduce p70S6 kinase phosphorylation. Inhibition of AMPK impaired autophagy activation and enhanced palmitate-induced apoptosis during rosiglitazone treatment. These findings reveal that rosiglitazone-induced autophagy contributes to its protective function on beta-cells during palmitate treatment.


Rosiglitazone Autophagy Palmitate AMPK



AMP-activated protein kinase


Transmission electron microscopy








Peroxisome proliferator-activated receptor-γ


Microtubule associated protein 1 light chain 3


4′,6′-Diamidino-2-phenylindole dihydrochloride


Mitogen-activated protein kinases

Supplementary material

12020_2012_9826_MOESM1_ESM.doc (95 kb)
Supplementary material 1 (DOC 95 kb)

Copyright information

© Springer Science+Business Media New York 2012