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大鼠骨骼肌微血管血管运动和肌源性反应降低与急性胰岛素抵抗相关。

Decreased microvascular vasomotion and myogenic response in rat skeletal muscle in association with acute insulin resistance.

作者信息

Newman John M B, Dwyer Renee M, St-Pierre Philippe, Richards Stephen M, Clark Michael G, Rattigan Stephen

机构信息

Menzies Research Institute, University of Tasmania, Hobart 7001, Australia.

出版信息

J Physiol. 2009 Jun 1;587(Pt 11):2579-88. doi: 10.1113/jphysiol.2009.169011. Epub 2009 Apr 29.

Abstract

In addition to increased glucose uptake, insulin action is associated with increased total and microvascular blood flow, and vasomotion in skeletal muscle. The aim of this study was to determine the effect of acute insulin resistance caused by the peripheral vasoconstrictor alpha-methylserotonin (alphaMT) on microvascular vasomotion in muscle. Heart rate (HR), mean arterial pressure (MAP), femoral blood flow (FBF), whole body glucose infusion (GIR) and hindleg glucose uptake (HGU) were determined during control and hyperinsulinaemic euglycaemic clamp conditions in anaesthetized rats receiving alphaMT infusion. Changes in muscle microvascular perfusion were measured by laser Doppler flowmetry (LDF) and vasomotion was assessed by applying wavelet analysis to the LDF signal. Insulin increased GIR and HGU. Five frequency bands corresponding to cardiac, respiratory, myogenic, neurogenic and endothelial activities were detected in the LDF signal. Insulin infusion alone increased FBF (1.18 +/- 0.10 to 1.78 +/- 0.12 ml min(-1), P < 0.05), LDF signal strength (by 16% compared to baseline) and the relative amplitude of the myogenic component of vasomotion (0.89 +/- 0.09 to 1.18 +/- 0.06, P < 0.05). When infused alone alphaMT decreased LDF signal strength and the myogenic component of vasomotion by 23% and 27% respectively compared to baseline, but did not affect HGU or FBF. Infusion of alphaMT during the insulin clamp decreased the stimulatory effects of insulin on GIR, HGU, FBF and LDF signal and blocked the myogenic component of vasomotion. These data suggest that insulin action to recruit microvascular flow may in part involve action on the vascular smooth muscle to increase vasomotion in skeletal muscle to thereby enhance perfusion and glucose uptake. These processes are impaired with this model of alphaMT-induced acute insulin resistance.

摘要

除了增加葡萄糖摄取外,胰岛素作用还与骨骼肌的总血流量、微血管血流量增加以及血管运动有关。本研究的目的是确定外周血管收缩剂α-甲基血清素(αMT)引起的急性胰岛素抵抗对肌肉微血管运动的影响。在接受αMT输注的麻醉大鼠中,在对照和高胰岛素正常血糖钳夹条件下测定心率(HR)、平均动脉压(MAP)、股血流量(FBF)、全身葡萄糖输注率(GIR)和后肢葡萄糖摄取量(HGU)。通过激光多普勒血流仪(LDF)测量肌肉微血管灌注的变化,并通过对LDF信号应用小波分析来评估血管运动。胰岛素增加了GIR和HGU。在LDF信号中检测到与心脏、呼吸、肌源性、神经源性和内皮活动相对应的五个频段。单独输注胰岛素可增加FBF(从1.18±0.10增至1.78±0.12 ml·min⁻¹,P<0.05)、LDF信号强度(与基线相比增加16%)以及血管运动肌源性成分的相对幅度(从0.89±0.09增至1.18±0.06,P<0.05)。单独输注αMT时,与基线相比,LDF信号强度和血管运动的肌源性成分分别降低了23%和27%,但不影响HGU或FBF。在胰岛素钳夹期间输注αMT可降低胰岛素对GIR、HGU、FBF和LDF信号的刺激作用,并阻断血管运动的肌源性成分。这些数据表明,胰岛素募集微血管血流的作用可能部分涉及对血管平滑肌的作用,以增加骨骼肌的血管运动,从而增强灌注和葡萄糖摄取。在这种αMT诱导的急性胰岛素抵抗模型中,这些过程受到损害。

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