Hokkaido University Collection of Scholarly and Academic Papers >
Hokkaido University Hospital >
Peer-reviewed Journal Articles, etc >
The role of glucokinase and insulin receptor substrate-2 in the proliferation of pancreatic beta cells induced by short-term high-fat diet feeding in mice
This item is licensed under:Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
Title: | The role of glucokinase and insulin receptor substrate-2 in the proliferation of pancreatic beta cells induced by short-term high-fat diet feeding in mice |
Authors: | Kitao, Naoyuki Browse this author | Nakamura, Akinobu Browse this author →KAKEN DB | Miyoshi, Hideaki Browse this author →KAKEN DB | Nomoto, Hiroshi Browse this author | Takahashi, Kiyohiko Browse this author | Omori, Kazuno Browse this author | Yamamoto, Kohei Browse this author | Cho, Kyu Yong Browse this author | Terauchi, Yasuo Browse this author | Atsumi, Tatsuya Browse this author →KAKEN DB |
Keywords: | Beta cell proliferation | Glucokinase | High-fat diet | Insulin receptor substrate-2 |
Issue Date: | Aug-2018 |
Publisher: | Elsevier |
Journal Title: | Metabolism |
Volume: | 85 |
Start Page: | 48 |
End Page: | 58 |
Publisher DOI: | 10.1016/j.metabol.2018.03.010 |
PMID: | 29544862 |
Abstract: | Objective: 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. |
Rights: | © 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/ | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
Type: | article (author version) |
URI: | http://hdl.handle.net/2115/75063 |
Appears in Collections: | 北海道大学病院 (Hokkaido University Hospital) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
|
Submitter: 中村 昭伸
|