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

• Published in: Endocrine Vol. 44; no. 1; pp. 87 - 98
• Main Authors: Wu, Jie, Wu, Jun-jie, Yang, Lin-jun, Wei, Li-xin, Zou, Da-jin
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.08.2013
• Subjects: AMP-Activated Protein Kinases - antagonists & inhibitors; AMP-Activated Protein Kinases - genetics; AMP-Activated Protein Kinases - metabolism; Animals; Autophagy - drug effects; Cell Death - drug effects; Cells, Cultured; Cytoprotection - drug effects; Diabetes; Drug Evaluation, Preclinical; Endocrinology; Enzyme Activation - drug effects; Humanities and Social Sciences; Hypoglycemic Agents - pharmacology; Insulin-Secreting Cells - drug effects; Insulin-Secreting Cells - physiology; Internal Medicine; Medicine; Medicine & Public Health; multidisciplinary; Original Article; Palmitic Acid - adverse effects; Rats; RNA, Small Interfering - pharmacology; Science; Thiazolidinediones - pharmacology; Rosiglitazone; AMPK; Autophagy; Palmitate
• ISSN: 1355-008X; 1559-0100
• 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.