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大鼠胰岛素抵抗与肌细胞内脂质水平之间的相关性

Correlation between insulin resistance and intramyocellular lipid levels in rats.

作者信息

Kuhlmann J, Neumann-Haefelin C, Belz U, Kramer W, Juretschke H-P, Herling A W

机构信息

Aventis Pharma Deutschland GmbH, 65926 Frankfurt a.M., Germany.

出版信息

Magn Reson Med. 2005 Jun;53(6):1275-82. doi: 10.1002/mrm.20501.

DOI:10.1002/mrm.20501
PMID:15906287
Abstract

Increased intramyocellular lipid (IMCL) content has been proposed as biomarker for insulin resistance (IR). An inverse correlation between IMCL and insulin sensitivity (IS) was found in nonathletic humans, whereas in animal models only a few validation studies have been performed. The aim of this study was to investigate the interrelation between IS indices determined by the glucose clamp technique (glucose disposal (GD), exogenous glucose infusion rates (GIR)) and IMCL content in the tibialis (TIB) and the soleus (SOL) muscle obtained by magnetic resonance spectroscopy in different rat models of IR. Diet-induced insulin-resistant Wistar rats as well as genetic disease models (ZDF rats) were used. In both muscles, elevated IMCL correlated with an impaired IS in all models of IR. The correlation of IMCL with both parameters for IS was comparable in TIB and SOL. The best fit between IMCL and IS was obtained using TIB and GIR data (r = -0.69, P < 0.001). Diabetic male ZDF rats exhibited comparatively low IMCL levels due to their catabolic state: exclusion of this group improved r. In summary, IMCL, especially in TIB, is a valid biomarker for IS in various rat models of IR with the advantage of a fast repeatable noninvasive measurement in individual animals.

摘要

细胞内脂质(IMCL)含量增加已被提议作为胰岛素抵抗(IR)的生物标志物。在非运动员人群中发现IMCL与胰岛素敏感性(IS)呈负相关,而在动物模型中,仅进行了少数验证研究。本研究的目的是通过磁共振波谱法,研究在不同IR大鼠模型中,由葡萄糖钳夹技术测定的IS指标(葡萄糖处置(GD)、外源性葡萄糖输注率(GIR))与胫肌(TIB)和比目鱼肌(SOL)中IMCL含量之间的相互关系。使用饮食诱导的胰岛素抵抗Wistar大鼠以及遗传疾病模型(ZDF大鼠)。在所有IR模型中,两块肌肉中升高的IMCL均与受损的IS相关。IMCL与IS的两个参数之间的相关性在TIB和SOL中相当。使用TIB和GIR数据获得IMCL与IS之间的最佳拟合(r = -0.69,P < 0.001)。糖尿病雄性ZDF大鼠由于其分解代谢状态而表现出相对较低的IMCL水平:排除该组可改善r值。总之,IMCL,尤其是TIB中的IMCL,是各种IR大鼠模型中IS的有效生物标志物,具有可在个体动物中快速重复进行非侵入性测量的优势。

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