胰岛素和肌纤维类型对链脲佐菌素诱导的糖尿病大鼠比目鱼肌中N-ε-（羧甲基）-赖氨酸积累的影响。
Influence of insulin and muscle fiber type in nepsilon-(carboxymethyl)-lysine accumulation in soleus muscle of rats with streptozotocin-induced diabetes mellitus.
作者信息
Snow LeAnn M, Thompson Ladora V
机构信息
Departmentof Physical Medicine and Rehabilitation, University of Minnesota, Minneapolis, MN 55455, USA.
出版信息
Pathobiology. 2009;76(5):227-34. doi: 10.1159/000228898. Epub 2009 Oct 2.
BACKGROUND
Nepsilon-(carboxymethyl)-lysine (CML) is an advanced glycation end product (AGE), the accumulation of which has been implicated in the etiology of diabetes complications. Skeletal muscle in diabetes demonstrates altered function, and increased accumulation of CML has been found in several fast-twitch muscles of diabetic animals.
OBJECTIVE
This study aims to explore the accumulation of CML in soleus (a slow muscle) in diabetic animals, with and without insulin therapy.
METHODS
Twenty-one rats were randomly divided into control and diabetes groups (DNI: diabetes without insulin; DI: diabetes with insulin; C: control). Diabetes was induced by intravenous administration of streptozotocin. At the end of the 12-week experimental period the soleus muscle was excised and snap frozen in liquid nitrogen. Muscle cross-sections were immunolabeled for CML. The number of CML-labeled muscle fibers was quantified; fibers were also evaluated for fiber types and cross-sectional areas.
RESULTS
The percentage of myofibers immunolabeling for CML was highest in the DNI group (13.8 +/- 2.5%), lower in the DI group (5.4 +/- 1.1%) and lowest in the C group (2.1 +/- 0.6%). Statistical analysis revealed that AGE accumulation was significantly greater in the DNI group than in both C and DI groups (p = 0.0002). There was no significant difference between C and DI groups. In the DNI animals, AGE-positive myofibers showed a higher percentage of fast fiber types than did the AGE-negative fibers (49.5 +/- 6.9 vs. 13.7 +/- 1.5%, p = 0.002). No differences existed in cross-sectional areas between AGE-positive and AGE-negative fibers within any group.
CONCLUSION
The greatest accumulation of AGE was in the soleus of the DNI group, and was significantly less in the DI group. These findings may be linked to disordered glucose metabolism, increased oxidative stress and/or fiber type transformation in these muscles.
背景
N-ε-(羧甲基)-赖氨酸（CML）是一种晚期糖基化终产物（AGE），其积累与糖尿病并发症的病因有关。糖尿病患者的骨骼肌功能发生改变，在糖尿病动物的几块快肌中发现CML的积累增加。
目的
本研究旨在探讨糖尿病动物比目鱼肌（慢肌）中CML的积累情况，以及胰岛素治疗对其的影响。
方法
将21只大鼠随机分为对照组和糖尿病组（DNI：未接受胰岛素治疗的糖尿病组；DI：接受胰岛素治疗的糖尿病组；C：对照组）。通过静脉注射链脲佐菌素诱导糖尿病。在12周实验期结束时，切除比目鱼肌并在液氮中速冻。对肌肉横截面进行CML免疫标记。对CML标记的肌纤维数量进行定量；还对纤维类型和横截面积进行评估。
结果
CML免疫标记的肌纤维百分比在DNI组最高（13.8±2.5%），在DI组较低（5.4±1.1%），在C组最低（2.1±0.6%）。统计分析显示，DNI组的AGE积累显著高于C组和DI组（p = 0.0002）。C组和DI组之间无显著差异。在DNI动物中，AGE阳性肌纤维中快纤维类型的百分比高于AGE阴性纤维（49.5±6.9对13.7±1.5%，p = 0.002）。任何组内AGE阳性和AGE阴性纤维的横截面积均无差异。
结论
AGE积累最多的是DNI组的比目鱼肌，DI组明显较少。这些发现可能与这些肌肉中葡萄糖代谢紊乱、氧化应激增加和/或纤维类型转变有关。
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