Metformin improves skeletal muscle microvascular insulin resistance in metabolic syndrome.
Metformin improves skeletal muscle microvascular insulin resistance in metabolic syndrome.
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DOI：
10.1152/ajpendo.00287.2021
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发表时间：
2022-02-01
期刊：
影响因子：
--
通讯作者：
Barrett EJ
中科院分区：
文献类型：
--
作者：
Jahn LA;Hartline L;Liu Z;Barrett EJ
微血管胰岛素抵抗存在于代谢综合征中，并可能导致心血管疾病风险增加和观察到的对胰岛素的代谢反应受损。二甲双胍改善人类的代谢胰岛素抵抗。其对大血管和微血管胰岛素抵抗的影响尚未确定。采用交叉设计，对11例非糖尿病代谢综合征受试者进行了4次研究（安慰剂或二甲双胍治疗12周前后），两次治疗之间的洗脱期为8周。在每种情况下，我们测量了大动脉功能的三个指标[脉搏波速度（PWV），桡动脉脉搏波分离分析（PWSA），肱动脉内皮功能（流量介导的扩张-FMD）]以及肌肉微血管灌注[造影剂增强超声（CEU）]之前和120分钟，1 mU/min/kg的正葡萄糖胰岛素钳夹。二甲双胍降低了体重指数（BMI）、脂肪重量和体脂百分比（P < 0.05），而安慰剂没有影响。二甲双胍（非安慰剂）改善了代谢性胰岛素敏感性（钳夹葡萄糖输注速率，P < 0.01），胰岛素后PWV和FMD不受二甲双胍治疗的影响。胰岛素组仅在二甲双胍治疗后PWSA改善（P < 0.01）。在安慰剂治疗前后和二甲双胍治疗前，胰岛素均降低了通过超声造影测量的肌肉微血管血容量（P < 0.02），但二甲双胍治疗后没有。短期二甲双胍治疗可改善代谢和肌肉微血管对胰岛素的反应。二甲双胍对微血管胰岛素反应性的作用可能有助于其有益的代谢作用。二甲双胍没有改善主动脉僵硬度或肱动脉内皮功能，但增强了桡动脉脉搏波特性，与小动脉舒张一致。新&值得注意的是，Metalloy是2型糖尿病的一线治疗药物，常用于胰岛素抵抗和代谢综合征患者。在此，我们首次提供了二甲双胍改善胰岛素抵抗人群肌肉微血管胰岛素敏感性的证据。同时，二甲双胍改善了肌肉葡萄糖的处理，支持胰岛素的微血管和肌肉代谢作用之间的密切关系。微血管胰岛素敏感性增强是否有助于二甲双胍减少糖尿病微血管并发症的能力仍有待解决。
Microvascular insulin resistance is present in metabolic syndrome and may contribute to increased cardiovascular disease risk and the impaired metabolic response to insulin observed. Metformin improves metabolic insulin resistance in humans. Its effects on macro and microvascular insulin resistance have not been defined. Eleven subjects with nondiabetic metabolic syndrome were studied four times (before and after 12 wk of treatment with placebo or metformin) using a crossover design, with an 8-wk washout interval between treatments. On each occasion, we measured three indices of large artery function [pulse wave velocity (PWV), radial pulse wave separation analysis (PWSA), brachial artery endothelial function (flow-mediated dilation-FMD)] as well as muscle microvascular perfusion [contrast-enhanced ultrasound (CEU)] before and at 120 min into a 150 min, 1 mU/min/kg euglycemic insulin clamp. Metformin decreased body mass index (BMI), fat weight, and % body fat (P < 0.05, each), however, placebo had no effect. Metformin (not placebo) improved metabolic insulin sensitivity, (clamp glucose infusion rate, P < 0.01), PWV, and FMD after insulin were unaffected by metformin treatment. PWSA improved with insulin only after metformin P < 0.01). Insulin decreased muscle microvascular blood volume measured by contrast ultrasound both before and after placebo and before metformin (P < 0.02 for each) but not after metformin. Short-term metformin treatment improves both metabolic and muscle microvascular response to insulin. Metformin’s effect on microvascular insulin responsiveness may contribute to its beneficial metabolic effects. Metformin did not improve aortic stiffness or brachial artery endothelial function, but enhanced radial pulse wave properties consistent with relaxation of smaller arterioles. NEW & NOTEWORTHY Metformin, a first-line treatment for type 2 diabetes, is often used in patients with insulin resistance and metabolic syndrome. Here, we provide the first evidence for metformin improving muscle microvascular insulin sensitivity in insulin-resistant humans. Simultaneously, metformin improved muscle glucose disposal, supporting a close relationship between insulin’s microvascular and its metabolic actions in muscle. Whether enhanced microvascular insulin sensitivity contributes to metformin’s ability to decrease microvascular complications in diabetes remains to be resolved.
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影响因子：
16.2
作者：
Isomaa, B;Almgren, P;Groop, L
通讯作者：
Groop, L
影响因子：
24
作者：
Chirinos, Julio A.;Kips, Jan G.;Jacobs, David R., Jr.;Brumback, Lyndia;Duprez, Daniel A.;Kronmal, Richard;Bluemke, David A.;Townsend, Raymond R.;Vermeersch, Sebastian;Segers, Patrick
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影响因子：
--
作者：
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CHRISTENSEN, NJ
影响因子：
9.8
作者：
Abbasi, F;Chu, JW;Reaven, GM
通讯作者：
Reaven, GM
影响因子：
5.8
作者：
Emanuel, Anna L.;de Clercq, Nicolien C.;Serne, Erik H.
通讯作者：
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