Insulin-mediated microvascular recruitment (IMVR) regulates delivery of insulin and glucose to insulin-sensitive tissues. We have previously proposed that perivascular adipose tissue (PVAT) controls vascular function through outside-to-inside communication and through vessel-to-vessel, or “vasocrine,” signaling. However, direct experimental evidence supporting a role of local PVAT in regulating IMVR and insulin sensitivity in vivo is lacking. Here, we studied muscles with and without PVAT in mice using combined contrast-enhanced ultrasonography and intravital microscopy to measure IMVR and gracilis artery diameter at baseline and during the hyperinsulinemic-euglycemic clamp. We show, using microsurgical removal of PVAT from the muscle microcirculation, that local PVAT depots regulate insulin-stimulated muscle perfusion and glucose uptake in vivo. We discovered direct microvascular connections between PVAT and the distal muscle microcirculation, or adipomuscular arterioles, the removal of which abolished IMVR. Local removal of intramuscular PVAT altered protein clusters in the connected muscle, including upregulation of a cluster featuring Hsp90ab1 and Hsp70 and downregulation of a cluster of mitochondrial protein components of complexes III, IV, and V. These data highlight the importance of PVAT in vascular and metabolic physiology and are likely relevant for obesity and diabetes.

中文翻译：

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血管周围脂肪组织通过脂肪肌小动脉控制胰岛素刺激的灌注、线粒体蛋白表达和肌肉中的葡萄糖摄取

胰岛素介导的微血管募集 (IMVR) 调节胰岛素和葡萄糖向胰岛素敏感组织的输送。我们之前曾提出，血管周围脂肪组织 (PVAT) 通过外到内的交流和血管到血管或“血管分泌”信号传导来控制血管功能。然而，缺乏支持局部 PVAT 在体内调节 IMVR 和胰岛素敏感性作用的直接实验证据。在这里，我们使用联合对比增强超声和活体显微镜研究了小鼠有和没有 PVAT 的肌肉，以测量基线和高胰岛素 - 正常血糖钳夹期间的 IMVR 和股薄动脉直径。我们表明，使用显微外科手术从肌肉微循环中去除 PVAT，局部 PVAT 库可调节体内胰岛素刺激的肌肉灌注和葡萄糖摄取。我们发现了 PVAT 与远端肌肉微循环或脂肪肌小动脉之间的直接微血管连接，去除这些微血管会消除 IMVR。局部去除肌内 PVAT 改变了连接肌肉中的蛋白质簇，包括上调以 Hsp90ab1 和 Hsp70 为特征的簇，以及下调复合物 III、IV 和 V 的线粒体蛋白组分簇。这些数据突出了 PVAT 在血管和代谢生理学，可能与肥胖和糖尿病有关。