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Deficiency in catechol-o-methyltransferase is linked to a disruption of glucose homeostasis in mice

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العنوان: Deficiency in catechol-o-methyltransferase is linked to a disruption of glucose homeostasis in mice
المؤلفون: Megumi Kanasaki, Swayam Prakash Srivastava, Fan Yang, Ling Xu, Sumiyo Kudoh, Munehiro Kitada, Norikazu Ueki, Hyoh Kim, Jinpeng Li, Satoru Takeda, Keizo Kanasaki, Daisuke Koya
المصدر: Scientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
بيانات النشر: Nature Portfolio, 2017.
سنة النشر: 2017
المجموعة: LCC:Medicine
LCC:Science
مصطلحات موضوعية: Medicine, Science
الوصف: Abstract 2-methoxyestradiol (2-ME), an estrogen metabolite generated via catechol-o-methyltransferase (COMT), is multifunctional methoxy-catechol. Here, we report that COMT deficiency leads to glucose intolerance and 2-ME rescues COMT-deficient-associated metabolic defects. Liver COMT protein was suppressed in high fat diet (HFD)-fed or in pregnant mice. COMT suppression, by Ro41-0960 or siRNA, in HFD fed mice or in pregnant mice exacerbated glucose intolerance; 2-ME intervention ameliorated these defects. 2-ME effects on glucose tolerance were associated with AMPK phosphorylation in the liver and in islet cells. Metformin restored liver COMT protein levels, and metformin-induced liver AMPK phosphorylation was abolished by COMT inhibition. The amelioration in glucose tolerance by 2-ME was associated with biphasic insulin secretion in an environment-dependent manner. 2-ME-induced insulin secretion was associated with the AMPK phosphorylation, PDX-1 phosphorylation, and MST-1 suppression in MIN-6 cells. Furthermore 2-ME displayed PPARγ agonist-like activity. These results suggest that COMT is an enzyme to maintain glucose homeostasis and 2-ME is a potential endogenous multi-target anti-diabetic candidate.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2045-2322
Relation: https://doaj.org/toc/2045-2322
DOI: 10.1038/s41598-017-08513-w
URL الوصول: https://doaj.org/article/b583bc08d06d4a32b024507f7393df70
رقم الأكسشن: edsdoj.b583bc08d06d4a32b024507f7393df70
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:20452322
DOI:10.1038/s41598-017-08513-w