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β-cell-protective effect of 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) as a glutamate dehydrogenase (GDH) activator in db/db mice
DC Field | Value | Language |
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dc.contributor.author | 한승진 | - |
dc.date.accessioned | 2015-12-24T08:38:47Z | - |
dc.date.available | 2015-12-24T08:38:47Z | - |
dc.date.issued | 2012 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/133892 | - |
dc.description | Dept. of Medicine/박사 | - |
dc.description.abstract | 2-Aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) is an activator of glutamate dehydrogenase (GDH), which is a mitochondrial enzyme with an important role in insulin secretion. We investigated the effect of BCH on the high glucose (HG)-induced reduction in glucose-stimulated insulin secretion (GSIS), the high glucose/palmitate (HG/PA)-induced reduction in insulin gene expression, and HG/PA-induced β-cell death. We also studied whether long-term treatment with BCH lowers blood glucose and improves β-cell integrity in db/db mice. We evaluated GSIS, insulin gene expression, and DNA fragmentation in INS-1 cells exposed to HG or HG/PA in the presence or absence of BCH. An in vivo study was performed, in which seven-week-old diabetic db/db mice were treated with BCH (0.7g/kg, n = 10) and with placebo (n = 10) every other day for 6 weeks. After treatment, an intraperitoneal glucose tolerance test and immunohistologic examinations were performed.Treatment with BCH blocked HG-induced GSIS inhibition and the HG/PA-induced reduction in insulin gene expression in INS-1 cells. In addition, BCH significantly reduced HG/PA-induced INS-1 cell death and phospho-JNK expression. BCH treatment improved glucose tolerance and insulin secretion in db/db mice. BCH treatment also increased the ratio of insulin-positive β-cells to total islet area (p < 0.05) and reduced the percentage of β-cells expressing cleaved caspase 3 (p < 0.05). In conclusion, the GDH activator BCH improved glycemic control in db/db mice. This anti-diabetic effect may be associated with improved insulin secretion, preserved islet architecture, and reduced β-cell apoptosis. | - |
dc.description.statementOfResponsibility | open | - |
dc.publisher | Graduate School, Yonsei University | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.title | β-cell-protective effect of 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) as a glutamate dehydrogenase (GDH) activator in db/db mice | - |
dc.title.alternative | db/ db 마우스에서 glutamate dehydrogenase (GDH) 활성제인 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH)의 베타세포 보호효과 | - |
dc.type | Thesis | - |
dc.contributor.alternativeName | Han, Seung Jin | - |
dc.type.local | Dissertation | - |
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