Physiologic hyperinsulinemia enhances human skeletal muscle perfusion by capillary recruitment
Physiologic hyperinsulinemia enhances human skeletal muscle perfusion by capillary recruitment
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DOI：
10.2337/diabetes.50.12.2682
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发表时间：
2001-12-01
期刊：
影响因子：
7.7
通讯作者：
Barrett, E
中科院分区：
文献类型：
--
作者：
Coggins, M;Lindner, J;Barrett, E
尽管进行了大量研究，胰岛素对血流的作用与葡萄糖代谢之间的关系仍不清楚。胰岛素引起的微血管灌注变化，与对总血流量的影响无关，可能是促进胰岛素代谢作用的重要变量。我们假设血浆胰岛素浓度的适度生理增量会改变人体骨骼肌的微血管灌注，并且可以使用超声造影（CEU）来评估这些变化，CEU是一种通过测量微血管血容量（MBV）和微血管流速（MFV）来量化流量的经过验证的方法。在第一个方案中，10 名健康、禁食的成年人在血糖正常的情况下通过肱动脉接受胰岛素 (0.05 mU . kg(-1) . min(-1)) 4 小时。在基线和胰岛素输注后，在连续静脉输注白蛋白微泡期间通过 CEU 测量 MBV 和 MFV，并对前臂深屈肌进行间歇谐波超声成像。在第二个方案中，17 名健康、禁食的成年人通过肱动脉接受 4 小时胰岛素（0.1 mU . kg(-1) . min(-1)，n = 9）或生理盐水（n = 8）输注。通过替代 CEU 技术评估这些受试者的微血管容量，该技术使用基线和输注 4 小时后动脉内推注白蛋白微泡。两种方案均在每个阶段测量肌肉葡萄糖摄取量、血浆胰岛素浓度和前臂总血流量。在方案 2 受试者中，测量 1-甲基黄嘌呤 (1-MX) 的组织提取量作为灌注毛细血管体积的指数。咖啡因会产生 1-MX 作为代谢物，在研究之前给这些受试者服用咖啡因以提高血浆 1-MX 水平。在方案 1 受试者中，在前臂总血流量没有显着变化的情况下，胰岛素增加了肌肉葡萄糖摄取（180%，P < 0.05）和 MBV（54%，P < 0.01），并降低了 MFV（-42%，P = 0.07）。在方案 2 受试者中，胰岛素增加了葡萄糖摄取（220%，P < 0.01）和微血管体积（45%，P < 0.05）与前臂总血流量相关的中度增加（P < 0.05）。使用前臂 1-MX 提取，我们观察到胰岛素治疗受试者毛细血管体积增加的趋势，尽管不显着。总之，血浆胰岛素浓度的适度生理增量增加了微血管血容量，表明微血管灌注的改变与毛细血管募集机制一致。微血管（毛细血管）体积的增加（尽管总血流量不变）表明，仅使用大容量血流量的测量无法完全理解胰岛素的血管和代谢作用之间的关系。
Despite intensive study, the relation between insulin's action on blood flow and glucose metabolism remains unclear. Insulin-induced changes in microvascular perfusion, independent from effects on total blood flow, could be an important variable contributing to insulin's metabolic action. We hypothesized that modest, physiologic increments in plasma insulin concentration alter microvascular perfusion in human skeletal muscle and that these changes can be assessed using contrast-enhanced ultrasound (CEU), a validated method for quantifying flow by measurement of microvascular blood volume (MBV) and microvascular flow velocity (MFV). In the first protocol, 10 healthy, fasting adults received insulin (0.05 mU . kg(-1) . min(-1)) via a brachial artery for 4 h under euglycemic conditions. At baseline and after insulin infusion, MBV and MFV were measured by CEU during continuous intravenous infusion of albumin microbubbles with intermittent harmonic ultrasound imaging of the forearm deep flexor muscles. In the second protocol, 17 healthy, fasting adults received a 4-h infusion of either insulin (0.1 mU . kg(-1) . min(-1), n = 9) or saline (n = 8)via a brachial artery. Microvascular volume was assessed in these subjects by an alternate CEU technique using an intra-arterial bolus injection of albumin microbubbles at baseline and after the 4-h infusion. With both protocols, muscle glucose uptake, plasma insulin concentration, and total blood flow to the forearm were measured at each stage. In protocol 2 subjects, tissue extraction of 1-methylxanthine (1-MX) was measured as an index of perfused capillary volume. Caffeine, which produces 1-MX as a metabolite, was administered to these subjects before the study to raise plasma 1-MX levels. In protocol 1 subjects, insulin increased muscle glucose uptake (180%, P < 0.05) and MBV (54%, P < 0.01) and decreased MFV (-42%, P = 0.07) in the absence of significant changes in total forearm blood flow.In protocol 2 subjects, insulin increased glucose uptake (220%, P < 0.01) and microvascular volume (45%, P < 0.05) with an associated moderate increase in total forearm blood flow (P < 0.05). Using forearm 1-MX extraction, we observed a trend, though not significant, toward increasing capillary volume in the insulin-treated subjects. In conclusion, modest physiologic increments in plasma insulin concentration increased microvascular blood volume, indicating altered microvascular perfusion consistent with a mechanism of capillary recruitment. The increases in microvascular (capillary) volume (despite unchanged total blood flow) indicate that the relation between insulin's vascular and metabolic actions cannot be fully understood using measurements of bulk blood flow alone.