title: Suppression of FoxO1/cell death-inducing DNA fragmentation factor α-like effector A (Cidea) axis protects mouse β-cells against palmitic acid-induced apoptosis.
abstract: Chronic exposure to free fatty acid (FFA) induces pancreatic β-cell apoptosis, which may contribute to the development of type 2 diabetes. The cell death-inducing DNA fragmentation factor α-like effector (CIDE) family is involved in type 2 diabetes with obesity. In the present study, we found that only apoptosis-inducing FFA upregulated Cidea, and both apoptosis and Cidea were upregulated most strongly by palmitic acid, suggesting that the expression of Cidea is positively correlated with apoptosis. In contrast, there were weak correlations between Cideb and Cidec expression, and apoptosis. Furthermore, suppression of Cidea inhibited palmitic acid-induced apoptosis. Finally, suppression of FoxO1 inhibited palmitic acid-induced Cidea upregulation and apoptosis. These results indicate that Cidea is a critical regulator of FFA-induced apoptosis as a novel downstream target for FoxO1 in β-cells, suggesting that suppression of Cidea is a potentially useful therapeutic approach for protecting against β-cell loss in type 2 diabetes.
authors.affiliation: Discovery Research Laboratories, Kyorin Pharmaceutical Co., Ltd., 2399-1 Nogi-machi, Shimotsuga-gun, Tochigi 329-0114, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Omae
authors.forename: Minoru
authors.initials: M
authors.lastname: Ito
authors.forename: Syoko
authors.initials: S
authors.lastname: Hase
authors.forename: Michiaki
authors.initials: M
authors.lastname: Nagasawa
authors.forename: Junichi
authors.initials: J
authors.lastname: Ishiyama
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Ide
authors.forename: Koji
authors.initials: K
authors.lastname: Murakami
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D053938:DNA Fragmentation; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019308:Palmitic Acid; D034622:RNA Interference; D046509:Tissue Culture Techniques
chemical_list: D051017:Apoptosis Regulatory Proteins; C112510:Cidea protein, mouse; D005230:Fatty Acids, Nonesterified; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; D019308:Palmitic Acid