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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

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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
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
Type: article (author version)
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

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