Other
12 Authors
- Kanasaki M,
- Takeda S,
- Kim H,
- Yang F,
- Koya D,
- Kudoh S,
- Kitada M,
- Xu L,
- Ueki N,
- Li J,
- Srivastava SP,
- Kanasaki K
| First Author | Kanasaki M | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Issue | 1 | Pages | 7927 |
| PubMed ID | 28801594 | Mgi Jnum | J:272158 |
| Mgi Id | MGI:6282638 | Doi | 10.1038/s41598-017-08513-w |
| Citation | Kanasaki M, et al. (2017) Deficiency in catechol-o-methyltransferase is linked to a disruption of glucose homeostasis in mice. Sci Rep 7(1):7927 |
| abstractText | 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 PPARgamma 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. |
