Item type |
デフォルトアイテムタイプ(フル)(1) |
公開日 |
2020-11-17 |
タイトル |
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タイトル |
Reintroducing testosterone in the db/db mouse partially restores normal glucose metabolism and insulin resistance in a leptin-independent manner |
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言語 |
en |
作成者 |
Yabiku, Koichi
Nakamoto, Keiko
Tokushige, Akihiro
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アクセス権 |
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アクセス権 |
open access |
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アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
権利情報 |
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言語 |
en |
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権利情報 |
Creative Commons Attribution 4.0 |
権利情報 |
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言語 |
en |
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権利情報Resource |
https://creativecommons.org/licenses/by/4.0/ |
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権利情報 |
https://creativecommons.org/licenses/by/4.0/ |
主題 |
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言語 |
en |
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主題Scheme |
Other |
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主題 |
Testosterone replacement |
主題 |
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言語 |
en |
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主題Scheme |
Other |
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主題 |
Leptin signal knockout |
主題 |
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言語 |
en |
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主題Scheme |
Other |
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主題 |
Aromatization |
主題 |
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言語 |
en |
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主題Scheme |
Other |
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主題 |
Impaired glucose tolerance |
主題 |
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言語 |
en |
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主題Scheme |
Other |
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主題 |
Fatty liver |
内容記述 |
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内容記述タイプ |
Other |
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内容記述 |
Background: Testosterone signals through the androgen receptor (AR) and AR knockout mice develop obesity, suggesting a functional association between AR and leptin signaling. Furthermore, physiological blood concentrations of testosterone have been found to inhibit the development of arteriosclerosis, obesity and diabetes. However, these findings have not been verified by testosterone replacement in animal models and whether or not testosterone acts directly by activating AR to enhance leptin signaling, or indirectly by its conversion into estrogen remains unclear. Therefore, we investigated the effect of exogenously supplemented testosterone on glucose and lipid metabolism.\nMethods: Four-week-old male leptin receptor-knockout db/db mice were used as controls for a model of obesity retaining low testosterone. Mice were divided into sham-operated, castrated, or castrated and testosterone-supplemented groups and fed a high-fat diet (HFD) for 2 weeks from 5 weeks of age. Testosterone concentrations, blood glucose, plasma insulin levels, and intraperitoneal glucose tolerance and insulin tolerance were measured. At 7 weeks, triglyceride and glycogen content were measured in the liver and muscle. Lipid accumulation in the liver and soleus muscle was determined by immunohistochemistry with Oil Red O. Statistical analyses were performed using the Student’s t-test or ANOVA where applicable.\nResults: Lower testosterone levels in db/db mice compared with wild type (WT) db/+ mice were associated with glucose intolerance and fatty liver. Furthermore, castrated male db/db mice at 4 weeks of age progressively developed glucose intolerance accompanying a 15% increase in liver fat. Male mice fed a HFD had lower levels of testosterone compared with those fed a normal diet. We found that exogenous testosterone replacement injected subcutaneously into castrated male db/db mice alleviated the exacerbation of fatty liver and glucose intolerance, suggesting a leptin-independent mechanism. This mechanism is most likely mediated through gonadal axis suppression in this mouse model.\nConclusions: In summary, testosterone may use a novel pathway to complement leptin signaling to regulate glucose and lipid metabolism, and thus offers a new therapeutic target to treat metabolic disorders. |
内容記述 |
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内容記述タイプ |
Other |
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内容記述 |
論文 |
出版者 |
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言語 |
en |
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出版者 |
BioMed Central |
言語 |
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言語 |
eng |
資源タイプ |
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資源タイプ |
journal article |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
出版タイプ |
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出版タイプ |
VoR |
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出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
識別子 |
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識別子 |
http://hdl.handle.net/20.500.12000/47252 |
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識別子タイプ |
HDL |
関連情報 |
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識別子タイプ |
DOI |
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関連識別子 |
https://doi.org/10.1186/s12902-018-0266-y |
関連情報 |
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識別子タイプ |
DOI |
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関連識別子 |
https://doi.org/10.1186/s12902-018-0266-y |
収録物識別子 |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
1472-6823 |
収録物名 |
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言語 |
en |
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収録物名 |
BMC Endocrine Disorders |
書誌情報 |
巻 18,
発行日 2018-06-13
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