title: Vanadyl bisacetylacetonate protects β cells from palmitate-induced cell death through the unfolded protein response pathway.
abstract: 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.
authors.affiliation: State Key Laboratories of Natural and Biomimetic Drugs and Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing, People's Republic of China.
authors.forename: Zhonglan
authors.initials: Z
authors.lastname: Gao
authors.forename: Chengyue
authors.initials: C
authors.lastname: Zhang
authors.forename: Siwang
authors.initials: S
authors.lastname: Yu
authors.forename: Xiaoda
authors.initials: X
authors.lastname: Yang
authors.forename: Kui
authors.initials: K
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D019610:Cytoprotection; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D006885:Hydroxybutyrates / Q000737:chemistry / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D010168:Palmitates / Q000378:metabolism*; D010422:Pentanones / Q000737:chemistry / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D056811:Unfolded Protein Response / Q000187:drug effects*; D014638:Vanadates / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D005230:Fatty Acids, Nonesterified; D006885:Hydroxybutyrates; D007328:Insulin; D010168:Palmitates; D010422:Pentanones; D017382:Reactive Oxygen Species; C049529:acetyl acetonate; D014638:Vanadates; D002118:Calcium