Endocrine

, Volume 44, Issue 1, pp 87–98 | Cite as

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

  • Jie Wu
  • Jun-jie Wu
  • Lin-jun Yang
  • Li-xin Wei
  • Da-jin Zou
Original Article

Abstract

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.

Keywords

Rosiglitazone Autophagy Palmitate AMPK 

Abbreviations

AMPK

AMP-activated protein kinase

TEM

Transmission electron microscopy

CQ

Chloroquine

3-MA

3-Methyladenine

TZDs

Thiazolidinediones

PPAR-γ

Peroxisome proliferator-activated receptor-γ

LC3

Microtubule associated protein 1 light chain 3

DAPI

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

MAPK

Mitogen-activated protein kinases

Notes

Acknowledgments

This project was supported by the Special Funds for National Natural Science Foundation of China (Grant No. 81070619), the Commission of Science and Technology of Shanghai Municipality (No. 08411967100).

Conflict of interest

We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of the manuscript entitled.

Supplementary material

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

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Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Jie Wu
    • 1
    • 2
  • Jun-jie Wu
    • 3
  • Lin-jun Yang
    • 4
  • Li-xin Wei
    • 5
  • Da-jin Zou
    • 1
  1. 1.Department of Endocrinology, Chang Hai HospitalThe Second Military Medical UniversityShanghaiPeople’s Republic of China
  2. 2.Department of Endocrinology, Tong Ji HospitalTong Ji UniversityShanghaiPeople’s Republic of China
  3. 3.National Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life SciencesFudan UniversityShanghaiPeople’s Republic of China
  4. 4.Department of Oncology, Chang Hai HospitalThe Second Military Medical UniversityShanghaiPeople’s Republic of China
  5. 5.Department of Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery HospitalThe Second Military Medical UniversityShanghaiPeople’s Republic of China

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