Muscle-specific vascular endothelial growth factor deletion induces muscle capillary rarefaction creating muscle insulin resistance.
Muscle-specific vascular endothelial growth factor deletion induces muscle capillary rarefaction creating muscle insulin resistance.
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DOI：
10.2337/db12-0354
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发表时间：
2013-02
期刊：
影响因子：
7.7
通讯作者：
Wasserman DH
中科院分区：
文献类型：
--
作者：
Bonner JS;Lantier L;Hasenour CM;James FD;Bracy DP;Wasserman DH
肌肉胰岛素抵抗与血管内皮生长因子（VEGF）作用和肌肉毛细血管密度降低有关。我们在C57 BL/6背景下，在骨骼肌和心肌VEGF缺失（mVEGF-/-）和野生型同窝小鼠（mVEGF+/+）中，检验了肌肉毛细血管稀疏对肌肉胰岛素抵抗病因学的重要作用这一假设。mVEGF−/−小鼠的骨骼肌和心肌毛细血管分别减少了60%和50%。mVEGF-/-小鼠的空腹血糖代谢率增加。胰岛素刺激的全身葡萄糖消失在mVEGF−/−小鼠中减弱。胰岛素刺激期间外周葡萄糖利用率降低是由于体内心脏和骨骼肌胰岛素作用和信号传导减少。胰岛素刺激的肌肉葡萄糖摄取减少与肌细胞胰岛素作用缺陷无关，表明胰岛素刺激的肌肉葡萄糖摄取受损是由于肌肉灌注不良。心肌中VEGF的缺失不影响心输出量。这些研究强调了靶向血管系统治疗胰岛素抵抗肌肉的新治疗方法的重要性。
Muscle insulin resistance is associated with a reduction in vascular endothelial growth factor (VEGF) action and muscle capillary density. We tested the hypothesis that muscle capillary rarefaction critically contributes to the etiology of muscle insulin resistance in chow-fed mice with skeletal and cardiac muscle VEGF deletion (mVEGF−/−) and wild-type littermates (mVEGF+/+) on a C57BL/6 background. The mVEGF−/− mice had an ∼60% and ∼50% decrease in capillaries in skeletal and cardiac muscle, respectively. The mVEGF−/− mice had augmented fasting glucose turnover. Insulin-stimulated whole-body glucose disappearance was blunted in mVEGF−/− mice. The reduced peripheral glucose utilization during insulin stimulation was due to diminished in vivo cardiac and skeletal muscle insulin action and signaling. The decreased insulin-stimulated muscle glucose uptake was independent of defects in insulin action at the myocyte, suggesting that the impairment in insulin-stimulated muscle glucose uptake was due to poor muscle perfusion. The deletion of VEGF in cardiac muscle did not affect cardiac output. These studies emphasize the importance for novel therapeutic approaches that target the vasculature in the treatment of insulin-resistant muscle.
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在四种常用的近交小鼠菌株中的体内葡萄糖代谢。
影响因子：
7.7
作者：
Berglund, Eric D.;Li, Candice Y.;Poffenberger, Greg;Ayala, Julio E.;Fueger, Patrick T.;Willis, Shannon E.;Jewell, Marybeth M.;Powers, Alvin C.;Wasserman, David H.
通讯作者：
Wasserman, David H.
影响因子：
5.4
作者：
Guo, Qi;Mori, Takefumi;Jiang, Yue;Hu, Chunyan;Ohsaki, Yusuke;Yoneki, Yoshimi;Nakamichi, Takashi;Ogawa, Susumu;Sato, Hiroshi;Ito, Sadayoshi
通讯作者：
Ito, Sadayoshi
影响因子：
5.8
作者：
Gudbjörnsdóttir, S;Sjöstrand, M;Lönnroth, P
通讯作者：
Lönnroth, P
影响因子：
2.9
作者：
GOLDEN, S;WALS, PA;KATZ, J
通讯作者：
KATZ, J
影响因子：
7.7
作者：
Chai W;Wang W;Dong Z;Cao W;Liu Z
通讯作者：
Liu Z