2024-03-29T09:32:34Zhttps://eprints.lib.hokudai.ac.jp/dspace-oai/requestoai:eprints.lib.hokudai.ac.jp:2115/750632022-11-17T02:08:08Zhdl_2115_20043hdl_2115_137The role of glucokinase and insulin receptor substrate-2 in the proliferation of pancreatic beta cells induced by short-term high-fat diet feeding in miceKitao, NaoyukiNakamura, AkinobuMiyoshi, HideakiNomoto, HiroshiTakahashi, KiyohikoOmori, KazunoYamamoto, KoheiCho, Kyu YongTerauchi, YasuoAtsumi, TatsuyaBeta cell proliferationGlucokinaseHigh-fat dietInsulin receptor substrate-2490Objective: We investigated whether glucokinase and insulin receptor substrate-2 were required for beta cell proliferation induced by short-term high-fat (HF) diet feeding, as has been shown for long-term HF diet. Methods: Eight-week-old C57BL/6J mice were exposed to either a standard chow (SC) or HF diet. After 1 week on the diet, histopathological beta cell proliferation and gene expression in isolated islets were examined. Additionally, 8-week-old beta cell-specific glucokinase haploinsufficient(Gck(+/-)) and Irs2 knockout (Irs2(-/-)) mice were exposed to either an SC or HF diet. Results: lmmunohistochemical analysis revealed that short-term HF diet feeding resulted in a significant increase in BrdU incorporation rate compared with SC consumption in wild-type mice. Western blot analysis demonstrated that Irs2 expression levels did not differ between the two diets. Moreover, there was a significant increase in the BrdU incorporation rate in the HF diet group compared with the SC group in both Gck(+/-) and Irs2(-/-) mice. Gene expression profiling of isolated islets from mice fed an HF diet for 1 week revealed that the expression levels of downstream genes of Foxm1 were coordinately upregulated. One week of HF diet feeding stimulated beta cell proliferation with Foxm1 upregulation in 48-week-old mice as well as in 8-week-old. Conclusions: The mechanism of pancreatic beta cell proliferation induced by short-term HF diet feeding in mice could involve a glucokinase- and Irs2-independent pathway. Our results suggest that the pathways that induce beta cell proliferation in response to short-term HF diet feeding may differ from those in response to sustained HF diet feeding.ElsevierJournal Articleapplication/vnd.openxmlformats-officedocument.presentationml.presentationapplication/pdfhttp://hdl.handle.net/2115/75063https://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/75063/2/Metabolism85_48-SupplFig.pptxhttps://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/75063/1/Metabolism85_48.pdf0026-0495Metabolism8548582018-08enginfo:pmid/29544862info:doi/10.1016/j.metabol.2018.03.010© 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/author