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Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Medicine / Faculty of Medicine >
Peer-reviewed Journal Articles, etc >
Glucokinase Inactivation Paradoxically Ameliorates Glucose Intolerance by Increasing beta-Cell Mass in db/db Mice
| Title: | Glucokinase Inactivation Paradoxically Ameliorates Glucose Intolerance by Increasing beta-Cell Mass in db/db Mice |
| Authors: | Omori, Kazuno Browse this author | | Nakamura, Akinobu Browse this author →KAKEN DB | | Miyoshi, Hideaki Browse this author | | Yamauchi, Yuki Browse this author | | Kawata, Shinichiro Browse this author | | Takahashi, Kiyohiko Browse this author | | Kitao, Naoyuki Browse this author | | Nomoto, Hiroshi Browse this author | | Kameda, Hiraku Browse this author | | Cho, Kyu Yong Browse this author | | Terauchi, Yasuo Browse this author | | Atsumi, Tatsuya Browse this author |
| Issue Date: | Apr-2021 |
| Publisher: | American Diabetes Association |
| Journal Title: | Diabetes |
| Volume: | 70 |
| Issue: | 4 |
| Start Page: | 917 |
| End Page: | 931 |
| Publisher DOI: | 10.2337/db20-0881 |
| Abstract: | Efficacy of glucokinase activation on glycemic control is limited to a short-term period. One reason might be related to excess glucose signaling by glucokinase activation toward beta-cells. In this study, we investigated the effect of glucokinase haploinsufficiency on glucose tolerance as well as beta-cell function and mass using a mouse model of type 2 diabetes. Our results showed that in db/db mice with glucokinase haploinsufficiency, glucose tolerance was ameliorated by augmented insulin secretion associated with the increase in beta-cell mass when compared with db/db mice. Gene expression profiling and immunohistochemical and metabolomic analyses revealed that glucokinase haploinsufficiency in the islets of db/db mice was associated with lower expression of stress-related genes, greater expression of transcription factors involved in the maintenance and maturation of beta-cell function, less mitochondrial damage, and a superior metabolic pattern. These effects of glucokinase haploinsufficiency could preserve beta-cell mass under diabetic conditions. These findings verified our hypothesis that optimizing excess glucose signaling in beta-cells by inhibiting glucokinase could prevent beta-cell insufficiency, leading to improving glucose tolerance in diabetes status by preserving beta-cell mass. Therefore, glucokinase inactivation in beta-cells, paradoxically, could be a potential strategy for the treatment of type 2 diabetes. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/81365 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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