Lipotoxicity induced intracellular lipid accumulation in pancreatic β cells, one of the strongest predictors for T2DM. The objective of this study is to explore the role of Cav-1 in intracellular lipid accumulation of β cells under lipotoxicity condition. Our data showed that Cav-1 silencing significantly reduced PA-induced intracellular triglyceride (TG) accumulation, enhanced autophagy and insulin secretion in NIT-1 cells and murine pancreatic islets. Further investigation found that Cav-1 depletion facilitated AMPK phosphorylation, decreased the expression of downstream lipogenic makers (SREBP-1c, FAS and ACC) and increased the expression of fatty acid oxidation maker (CPT-1), leading to the ultimate enhancement of lipid metabolism. Meanwhile, Cav-1 depletion also suppressed mTOR phosphorylation, decreased the expression of p62 protein and increased the expression of LC3-II proteins, resulting in the ultimate increase of autophagy. Subsequent inhibition of AMPK and mTOR pathways abolished Cav-1 depletion mediated autophagy enhancement and TG content reduction, leading to the reduction of insulin secretion. Our findings suggest the potential application of the Cav-1 molecule as a target for effective T2DM treatment through preservation of lipotoxicity-induced β-cell intracellular lipid accumulation and dysfunction.

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Disclosure

W. Zeng: None. K. Liu: None. J. Tang: None. H. Peng: None. C. Lin: None. S. Lin: None. K. Lin: None. Y. Jiang: None. L. Zeng: None.

© 2018 by the American Diabetes Association.
2018
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