Intramyocellular lipid and insulin resistance -: A longitudinal in vivo 1H-spectroscopic study in Zucker diabetic fatty rats
Intramyocellular lipid and insulin resistance -: A longitudinal in vivo 1H-spectroscopic study in Zucker diabetic fatty rats
复制标题
DOI：
10.2337/diabetes.52.1.138
复制
发表时间：
2003-01-01
期刊：
影响因子：
7.7
通讯作者：
Herling, AW
中科院分区：
文献类型：
--
作者：
Kuhlmann, J;Neumann-Haefelin, C;Herling, AW
胰岛素抵抗在2型糖尿病的发病机制中起着重要作用。在人类中，胰岛素敏感性和肌细胞内脂质（IMCL）含量之间呈负相关;因此，IMCL成为胰岛素抵抗的标志物。最近，磁共振波谱（MRS）已被确立为一种可靠的方法，选择性检测和定量IMCL在人类。为了验证2型糖尿病动物模型中胰岛素敏感性和IMCL之间的相互关系，我们建立了7特斯拉的体积选择性H-1-MRS，以非侵入性评估大鼠IMCL。在雄性肥胖Zucker糖尿病肥胖大鼠及其同窝出生的瘦大鼠中，在4个月内重复测定IMCL水平，并在6-7周龄和22-24周龄时通过正常血糖-高胰岛素钳夹法测量胰岛素敏感性。IMCL和胰岛素敏感性之间的一个显着的关系，以及年龄依赖性的两个参数。罗格列酮治疗引起IMCL和肝脏脂肪明显减少，尽管体重增加，胰岛素敏感性显着改善。因此，罗格列酮的胰岛素增敏特性与脂质从非脂肪细胞（骨骼肌、肝脏）重新分配回脂肪组织一致。
Insulin resistance plays an important role in the pathogenesis of human type 2 diabetes. In humans, a negative correlation between insulin sensitivity and intramyocellular lipid (IMCL) content has been shown; thus, IMCL becomes a marker for insulin resistance. Recently, magnetic resonance spectroscopy (MRS) has been established as a dependable method for selective detection and quantification of IMCL in humans. To validate the interrelation between insulin sensitivity and IMCL in an animal model of type 2 diabetes, we established volume selective H-1-MRS at 7 Tesla to noninvasively assess IMCL in the rat. In male obese Zucker Diabetic Fatty rats and their lean littermates, IMCL levels were determined repeatedly over 4 months, and insulin sensitivity was measured by the euglycemic-hyperinsulinemic clamp method at 6-7 and at 22-24 weeks of age. A distinct relation between IMCL and insulin sensitivity was demonstrated as well as age dependence for both parameters. Rosiglitazone treatment caused a clear reduction of IMCL and hepatic fat despite increased body weight, and a marked improvement of insulin sensitivity. Thus, the insulin sensitizing properties of rosiglitazone were consistent with a redistribution of lipids from nonadipocytic (skeletal muscle, liver) back into fat tissue.