The regeneration of β-cell mass and preservation of its endocrine function under lipotoxicity are long-sought goals in diabetes research. Membrane protein caveolin-1 (Cav-1) is related to β-cell apoptosis and insulin secretion, however, the underlying mechanisms still remains unclear.

Our objective is to explore whether Cav-1 depletion protects pancreatic β cells from lipotoxicity and investigate the related mechanisms. Here, we found that Cav-1 silencing significantly promoted β-cell proliferation, inhibited palmitate (PA)-induced apoptosis and enhanced insulin production and secretion. These effects were associated with enhanced phosphorylation of Akt and ERK1/2 protein, which then downregulated the expression of cell cycle inhibitors (FOXO1, GSK3β, P21, P27 and P53) and upregulated Cyclin D2 and Cyclin D3 expression. Subsequent inhibition of PI3K/Akt and ERK/MAPK pathways abolished Cav-1 depletion induced β-cell mass protection. Furthermore,under PA enhanced endoplasmic reticulum (ER) stress, Cav-1 silencing significantly reduced eIF2α phosphorylation and expression of ER stress-responsive markers BiP and CHOP, which mediated the sensitization to lipotoxicity. 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 dysfunction and mass reduction.

W. Zeng: None. K. Liu: None. J. Tang: None. H. Li: None. H. Xu: None. H. Lu: None. H. Peng: None. C. Lin: None. R. Gao: None. S. Lin: None. K. Lin: None. Y. Jiang: None. L. Zeng: None.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at