Sonodynamic therapy inhibits palmitate-induced beta cell dysfunction via PINK1/Parkin-dependent mitophagy.

Abstract

In type 2 diabetes mellitus (T2DM), the overload of glucose and lipids can promote oxidative stress and inflammatory responses and contribute to the failure of beta cells. However, therapies that can modulate the function of beta cells and thus prevent their failure have not been well explored. In this study, beta cell injury model was established with palmitic acid (PA) to simulate the lipotoxicity (high-fat diet) found in T2DM. Sonodynamic therapy (SDT), a novel physicochemical treatment, was applied to treat injured beta cells. We found that SDT had specific effects on mitochondria and induced transient large amount of mitochondrial reactive oxygen species (ROS) production in beta cells. SDT also improved the morphology and function of abnormal mitochondria, inhibited inflammatory response and reduced beta cell dysfunction. The improvement of mitochondria was mediated by PINK1/Parkin-dependent mitophagy. Additionally, SDT rescued the transcription of PINK1 mRNA which was blocked by PA treatment, thus providing abundant PINK1 for mitophagy. Moreover, SDT also increased insulin secretion from beta cells. The protective effects of SDT were abrogated when mitophagy was inhibited by cyclosporin A (CsA). In summary, SDT potently inhibits lipotoxicity-induced beta cell failure via PINK1/Parkin-dependent mitophagy, providing theoretical guidance for T2DM treatment in aspects of islet protection.

• Authors: Tian Guo, Tianyang Liu, Yun Sun, Xianna Liu, Rongguo Xiong, He Li, Zhitao Li, Zhiguo Zhang, Zhen Tian, Ye Tian
• Journal: Cell death & disease (Cell Death Dis) Vol. 10 Issue 6 Pg. 457 (06 11 2019) ISSN: 2041-4889 [Electronic] England
• PMID: 31186419 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carrier Proteins
• Protoporphyrins
• Reactive Oxygen Species
• Receptors, GABA-A
• Tspo protein, rat
• Palmitic Acid
• protoporphyrin IX
• Ubiquitin-Protein Ligases
• parkin protein
• Protein Kinases
• PTEN-induced putative kinase

Topics

• Animals
• Carrier Proteins (metabolism)
• Cell Line
• Cell Survival (drug effects, genetics, radiation effects)
• Diabetes Mellitus, Type 2 (metabolism, therapy)
• Inflammation (metabolism, radiotherapy)
• Insulin-Secreting Cells (drug effects, metabolism, radiation effects)
• Mitochondria (genetics, metabolism, radiation effects, ultrastructure)
• Mitophagy (drug effects, genetics, radiation effects)
• Palmitic Acid (pharmacology, toxicity)
• Protein Kinases (genetics, metabolism)
• Protoporphyrins (metabolism)
• Rats
• Reactive Oxygen Species (metabolism)
• Receptors, GABA-A (metabolism)
• Ubiquitin-Protein Ligases (genetics, metabolism)
• Ultrasonic Waves