OBJECTIVE Obesity is associated with microvascular insulin resistance, which is characterized by impaired insulin-mediated microvascular recruitment. Glucagon-like peptide 1 (GLP-1) recruits skeletal and cardiac muscle microvasculature, and this action is preserved in insulin-resistant rodents. We aimed to examine whether GLP-1 recruits microvasculature and improves the action of insulin in obese humans. RESEARCH DESIGN AND METHODS Fifteen obese adults received intravenous infusion of either saline or GLP-1 (1.2 pmol/kg/min) for 150 min with or without a euglycemic insulin clamp (1 mU/kg/min) superimposed over the last 120 min. Skeletal and cardiac muscle microvascular blood volume (MBV), flow velocity and blood flow, brachial artery diameter and blood flow, and pulse wave velocity (PWV) were determined. RESULTS Insulin failed to change MBV or flow in either skeletal or cardiac muscle, confirming the presence of microvascular insulin resistance. GLP-1 infusion alone increased MBV by ∼30% and ∼40% in skeletal and cardiac muscle, respectively, with no change in flow velocity, leading to a significant increase in microvascular blood flow in both skeletal and cardiac muscle. Superimposition of insulin to GLP-1 infusion did not further increase MBV or flow in either skeletal or cardiac muscle but raised the steady-state glucose infusion rate by ∼20%. Insulin, GLP-1, and GLP-1 + insulin infusion did not alter brachial artery diameter and blood flow or PWV. The vasodilatory actions of GLP-1 are preserved in both skeletal and cardiac muscle microvasculature, which may contribute to improving metabolic insulin responses and cardiovascular outcomes. CONCLUSIONS In obese humans with microvascular insulin resistance, GLP-1's vasodilatory actions are preserved in both skeletal and cardiac muscle microvasculature, which may contribute to improving metabolic insulin responses and cardiovascular outcomes.

中文翻译：

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胰高血糖素样肽 1 的血管舒张作用在骨骼肌和心肌微脉管系统中得以保留，但在具有血管胰岛素抵抗的肥胖人群的导管动脉中则不然。


目的 肥胖与微血管胰岛素抵抗相关，其特点是胰岛素介导的微血管募集受损。胰高血糖素样肽 1 (GLP-1) 募集骨骼和心肌微血管系统，这种作用在胰岛素抵抗的啮齿动物中得以保留。我们的目的是检查 GLP-1 是否募集微血管系统并改善肥胖人群中胰岛素的作用。研究设计和方法 15 名肥胖成人接受静脉输注生理盐水或 GLP-1 (1.2 pmol/kg/min) 150 分钟，在最后 120 分钟内叠加或不叠加正常血糖胰岛素钳夹 (1 mU/kg/min)。测定骨骼和心肌微血管血量（MBV）、流速和血流量、肱动脉直径和血流量以及脉搏波速度（PWV）。结果 胰岛素未能改变骨骼肌或心肌的 MBV 或血流，证实了微血管胰岛素抵抗的存在。单独输注 GLP-1 可使骨骼肌和心肌的 MBV 分别增加约 30% 和约 40%，而流速没有变化，导致骨骼肌和心肌的微血管血流量显着增加。将胰岛素与 GLP-1 输注叠加并没有进一步增加骨骼肌或心肌的 MBV 或血流，但使稳态葡萄糖输注率提高约 20%。胰岛素、GLP-1 和 GLP-1 + 胰岛素输注不会改变肱动脉直径和血流量或 PWV。 GLP-1 的血管舒张作用保留在骨骼和心肌微血管中，这可能有助于改善代谢胰岛素反应和心血管结局。 结论 在患有微血管胰岛素抵抗的肥胖人群中，GLP-1 的血管舒张作用在骨骼和心肌微血管中得以保留，这可能有助于改善代谢胰岛素反应和心血管结局。