Vanadyl bisacetylacetonate protects β cells from palmitate-induced cell death through the unfolded protein response pathway.

Endoplasmic reticulum (ER) stress induced by free fatty acids (FFA) is important to β-cell loss during the development of type 2 diabetes. To test whether vanadium compounds could influence ER stress and the responses in their mechanism of antidiabetic effects, we investigated the effects and the mechanism of vanadyl bisacetylacetonate [VO(acac)(2)] on β cells upon treatment with palmitate, a typical saturated FFA. The experimental results showed that VO(acac)(2) could enhance FFA-induced signaling pathways of unfolded protein responses by upregulating the prosurvival chaperone immunoglobulin heavy-chain binding protein/78-kDa glucose-regulated protein and downregulating the expression of apoptotic C/EBP homologous protein, and consequently the reduction of insulin synthesis. VO(acac)(2) also ameliorated FFA-disturbed Ca(2+) homeostasis in β cells. Overall, VO(acac)(2) enhanced stress adaption, thus protecting β cells from palmitate-induced apoptosis. This study provides some new insights into the mechanisms of antidiabetic vanadium compounds.