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Endocrine
Erschienen in: Endocrine 1/2013

01.08.2013 | Original Article

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

Erschienen in: Endocrine | Ausgabe 1/2013

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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.
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Metadaten
Titel
Rosiglitazone protects against palmitate-induced pancreatic beta-cell death by activation of autophagy via 5′-AMP-activated protein kinase modulation
Publikationsdatum
01.08.2013
Erschienen in
Endocrine / Ausgabe 1/2013
Print ISSN: 1355-008X
Elektronische ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-012-9826-5

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