Ablation of Rnf213 retards progression of diabetes in the Akita mouse
Ablation of Rnf213 retards progression of diabetes in the Akita mouse
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DOI：
10.1016/j.bbrc.2013.02.015
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发表时间：
2013-03-15
影响因子：
3.1
通讯作者：
Koizumi, Akio
中科院分区：
文献类型：
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作者：
Kobayashi, Hatasu;Yamazaki, Satoru;Koizumi, Akio
烟雾病（MMD）和烟雾病综合征是以 Willis 环及其分支进行性狭窄为特征的血管疾病。 RNF213 基因编码一类新型蛋白质，具有 E3 连接酶和 AAA + ATP 酶活性，已被确定为 MMD 的易感基因。然而，其生理功能仍不清楚。 MMD 和烟雾病综合征常伴有糖尿病。在这项研究中，我们产生了Rnf213敲除（KO）C57BL/6小鼠（Rnf213（-/-）；Ins2（+/+）），将其与秋田（C57BL/6 Rnf213（+/+）；Ins2（+/C96Y））小鼠（一种在5周龄时自发发展为糖尿病的品系）交配，以获得缺乏Rnf213并携带Rnf213的小鼠。秋田突变（KO/秋田，Rnf213(-/-)；Ins2(+/C96Y)）。 6至20周期间测量体重和血糖浓度。在 18 周龄时评估葡萄糖耐量、胰岛素抵抗、血浆胰岛素和瘦素浓度、食物消耗、胰腺胰岛素含量和组织病理学。我们发现，与秋田小鼠相比，KO/秋田小鼠的葡萄糖耐量（AUC 所示）降低了 20%（p < 0.05），胰腺中的胰岛素含量高出 150%（p < 0.05）。与秋田小鼠相比，KO/秋田小鼠通过组织病理学检查测定的 CHOP 阳性 β 细胞数量降低了 30%，食物消耗降低了 34%（各 p < 0.05）。这些发现表明，Rnf213 的破坏通过保护胰岛β细胞来改善葡萄糖耐量。 (C) 2013 Elsevier Inc. 保留所有权利。
Moyamoya disease (MMD) and moyamoya syndrome are vasculopathies characterized by progressive stenosis in the circle of Willis and its branches. The RNF213 gene, which encodes a novel class of proteins, characterized by both E3 ligase and AAA + ATPase activities, has been identified as the susceptibility gene for MMD. However, its physiological functions remain unknown. MMD and moyamoya syndrome are often accompanied by diabetes mellitus. In this study, we generated Rnf213 knockout (KO) C57BL/6 mice (Rnf213(-/-); Ins2(+/+)), which were mated with Akita (C57BL/6 Rnf213(+/+); Ins2(+/C96Y)) mice, a strain that develops diabetes spontaneously by 5 weeks of age, to obtain mice lacking Rnf213 and carrying the Akita mutation (KO/Akita, Rnf213(-/-); Ins2(+/C96Y)). Body weight and blood glucose concentration were measured from 6 to 20 weeks. Glucose tolerance, insulin resistance, plasma insulin and leptin concentrations, food consumption, pancreatic insulin content and histopathology were evaluated at 18 weeks of age. We found that glucose tolerance, as indicated by AUC, was 20% lower (p < 0.05) and insulin contents in pancreas were 150% higher (p < 0.05), in KO/Akita than in Akita mice. The number of CHOP positive beta-cells assayed by histopathological examination was 30% lower and food consumption was 34% lower in KO/Akita than in Akita mice (p < 0.05 each). These findings indicated that the disruption of Rnf213 improved glucose tolerance by protecting islet beta cells. (C) 2013 Elsevier Inc. All rights reserved.