Eskens Bart J M, Leurgans Thomas M, Vink Hans, Vanteeffelen Jurgen W G E
Department of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
Physiol Rep. 2014 Jan 6;2(1):e00194. doi: 10.1002/phy2.194. eCollection 2014 Jan 1.
While previous studies have indicated an important role for the endothelial glycocalyx in regulation of microvascular function, it was recently shown that acute enzymatic glycocalyx degradation in rats was associated with an impaired insulin-mediated glucose disposal. The aim of this study was to determine whether glycocalyx damage in skeletal muscle occurs at an early stage of diet-induced obesity (DIO). The microcirculation of the hindlimb muscle of anesthetized C57Bl/6 mice, fed chow (CON) or a high-fat diet (HFD) for 6 and 18 weeks (w), respectively, was visualized with a Sidestream Dark-Field camera, and glycocalyx barrier properties were derived from the calculated perfused boundary region (PBR). Subsequently, an intraperitoneal glucose tolerance test was performed and the area under the curve (AUC) of blood glucose was calculated. Impairment of glycocalyx barrier properties was already apparent after 6 weeks of HFD and remained after 18 weeks of HFD (PBR [in μm]: 0.81 ± 0.03 in CON_6w vs. 0.97 ± 0.04 in HFD_6w and 1.02 ± 0.07 in HFD_18w [both P < 0.05]). Glucose intolerance appeared to develop more slowly (AUC [in mmol/L × 120 min]: 989 ± 61 in CON_6w vs. 1204 ± 89 in HFD_6w [P = 0.11] and 1468 ± 84 in HFD_18w [P < 0.05]) than the impairment of glycocalyx barrier properties. The data indicate that damage to the endothelial glycocalyx is an early event in DIO. It is suggested that glycocalyx damage may contribute to the development of insulin resistance in obesity.
虽然先前的研究表明内皮糖萼在微血管功能调节中起重要作用，但最近有研究表明，大鼠急性酶促糖萼降解与胰岛素介导的葡萄糖处置受损有关。本研究的目的是确定饮食诱导肥胖（DIO）早期骨骼肌中是否发生糖萼损伤。分别用普通饲料（CON）或高脂饮食（HFD）喂养6周和18周的麻醉C57Bl/6小鼠后肢肌肉的微循环，用侧流暗场相机进行可视化观察，并从计算出的灌注边界区域（PBR）得出糖萼屏障特性。随后，进行腹腔内葡萄糖耐量试验，并计算血糖曲线下面积（AUC）。高脂饮食6周后糖萼屏障特性的损害已经很明显，高脂饮食18周后仍然存在（PBR[单位：μm]：CON_6w组为0.81±0.03，HFD_6w组为0.97±0.04，HFD_18w组为1.02±0.07[两者P<0.05]）。葡萄糖不耐受的发展似乎比糖萼屏障特性的损害更慢（AUC[单位：mmol/L×120分钟]：CON_6w组为989±61，HFD_6w组为1204±89[P=0.11]；HFD_18w组为1468±84[P<0.05]）。数据表明，内皮糖萼损伤是饮食诱导肥胖中的早期事件。提示糖萼损伤可能促成肥胖中胰岛素抵抗的发展。
