Glucagon-like peptide 1 recruits microvasculature and increases glucose use in muscle via a nitric oxide-dependent mechanism.

Glucagon-like peptide 1 recruits microvasculature and increases glucose use in muscle via a nitric oxide-dependent mechanism.
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DOI:
10.2337/db11-1073
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发表时间:
2012-04
期刊:
影响因子:
7.7
通讯作者:
Liu Z
Liu Z
中科院分区:
医学1区
文献类型:
--
作者:
Chai W;Dong Z;Wang N;Wang W;Tao L;Cao W;Liu Z

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胰高血糖素样肽1(GLP-1)增加组织葡萄糖摄取并引起不依赖于胰岛素的血管舒张。我们研究了GLP-1对肌肉微血管和葡萄糖摄取的影响。在确认GLP-1有效刺激内皮细胞中的一氧化氮(NO)合酶(NOS)磷酸化后,过夜禁食的成年雄性大鼠接受连续GLP-1输注(30 pmol/kg/min)2 h+或-NOS抑制。测定肌肉微血管血容量(MBV)、微血管血流速度(MFV)和微血管血流量(MBF)。另外的大鼠接受GLP-1或盐水30分钟,并测定肌肉胰岛素清除/摄取。GLP-1在30 min内急性增加肌肉MBV(P < 0.04),而不改变MFV或股血流量。这种作用在整个120分钟输注期间持续存在,导致肌肉MBF增加两倍以上(P < 0.02)。这些变化与血浆NO水平、肌肉间质氧饱和度、后腿葡萄糖提取和肌肉胰岛素清除/摄取的增加相一致。NOS抑制阻断了GLP-1介导的肌肉MBV、葡萄糖处置、NO产生和肌肉胰岛素清除/摄取的增加。总之,GLP-1通过NO依赖性机制急性募集微血管并增加肌肉中的基础葡萄糖摄取。因此,GLP-1可能通过扩大微血管内皮表面积来改善肌肉胰岛素作用。
Glucagon-like peptide 1 (GLP-1) increases tissue glucose uptake and causes vasodilation independent of insulin. We examined the effect of GLP-1 on muscle microvasculature and glucose uptake. After confirming that GLP-1 potently stimulates nitric oxide (NO) synthase (NOS) phosphorylation in endothelial cells, overnight-fasted adult male rats received continuous GLP-1 infusion (30 pmol/kg/min) for 2 h plus or minus NOS inhibition. Muscle microvascular blood volume (MBV), microvascular blood flow velocity (MFV), and microvascular blood flow (MBF) were determined. Additional rats received GLP-1 or saline for 30 min and muscle insulin clearance/uptake was determined. GLP-1 infusion acutely increased muscle MBV (P < 0.04) within 30 min without altering MFV or femoral blood flow. This effect persisted throughout the 120-min infusion period, leading to a greater than twofold increase in muscle MBF (P < 0.02). These changes were paralleled with increases in plasma NO levels, muscle interstitial oxygen saturation, hind leg glucose extraction, and muscle insulin clearance/uptake. NOS inhibition blocked GLP-1–mediated increases in muscle MBV, glucose disposal, NO production, and muscle insulin clearance/uptake. In conclusion, GLP-1 acutely recruits microvasculature and increases basal glucose uptake in muscle via a NO-dependent mechanism. Thus, GLP-1 may afford potential to improve muscle insulin action by expanding microvascular endothelial surface area.
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