The methionine-choline deficient dietary model of steatohepatitis does not exhibit insulin resistance
The methionine-choline deficient dietary model of steatohepatitis does not exhibit insulin resistance
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DOI：
10.1016/j.jhep.2003.09.020
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发表时间：
2004-01-01
影响因子：
25.7
通讯作者：
Green, RM
中科院分区：
文献类型：
--
作者：
Rinella, ME;Green, RM
背景目的：非酒精性脂肪性肝炎是一种重要的疾病，其病理生理学仍不完全清楚，尽管在人类中存在与胰岛素抵抗的强烈关联。喂食甲硫氨酸-胆碱缺乏（MCD）饮食的小鼠发生脂肪性肝炎，但胰岛素在此模型中的影响是unknown.Methods：雄性FVB/NJ小鼠喂食MCD、MCD对照或普通饲料10或28天。测定空腹血糖、ALT、甘油三酯和胰岛素。进行葡萄糖耐量试验（GTT）和胰岛素耐量试验（ITT），然后进行定量胰岛素敏感性检查指数（QUICKI）determination.Results：MCD组ALT水平显著升高。喂食MCD饲料的小鼠的空腹血糖为81 +/- 5 mg/dl，与MCD对照组（196 +/- 46 mg/dl）和饲料组（199 +/- 15 mg/dl）相比（P < 0.0001）。在GTT和ITT期间，葡萄糖给药对血糖的影响减弱，MCD组的胰岛素效应更明显（P = 0.026和P < 0.001）。QUICKI在喂食MCD的小鼠中显著高于喂食普通饲料的小鼠。结论：GTT、ITT和QUICKI证实喂食MCD的小鼠中不存在胰岛素抵抗。该模型导致纤维化脂肪性肝炎，并可能有助于描述人类脂肪性肝炎中涉及的非胰岛素抵抗机制。(C)2003年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
Background Aims: Non-alcoholic steatohepatitis is an important disease whose pathophysiology remains incompletely understood, although in humans a strong association with insulin resistance exists. Mice fed a methionine-choline deficient (MCD) diet develop steatohepatitis, however the influence of insulin in this model is unknown.Methods: Male FVB/NJ mice were fed the MCD, MCD control or chow diet for 10 or 28 days. Fasting glucose, ALT, triglyceride and insulin was measured. Glucose tolerance tests (GTT) and insulin tolerance tests (ITT) were performed followed by quantitative insulin sensitivity check index (QUICKI) determination.Results: ALT levels were significantly higher in the MCD group. Fasting glucose was 81 +/- 5 mg/dl in MCD diet fed mice, compared to MCD controls (196 +/- 46 mg/dl) and chow (199 +/- 15 mg/dl) (P < 0.0001). During GTT and ITT, the effect of glucose administration on blood glucose was dampened, and the insulin effect more pronounced in the MCD group (P = 0.026 and P < 0.001). QUICKI in MCD fed mice was significantly higher than in the chow fed mice.Conclusions: GTT, ITT and QUICKI confirmed the absence of insulin resistance in the MCD fed mice. This model causes fibrosing steatohepatitis and may help delineate the non-insulin resistant mechanisms involved in human steatohepatitis. (C) 2003 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.