Intracoronary glucagon-like peptide 1 preferentially augments glucose uptake in ischemic myocardium independent of changes in coronary flow.
Intracoronary glucagon-like peptide 1 preferentially augments glucose uptake in ischemic myocardium independent of changes in coronary flow.
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DOI：
10.1258/ebm.2011.011288
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发表时间：
2012-03
期刊：
影响因子：
--
通讯作者：
Tune JD
中科院分区：
文献类型：
--
作者：
Moberly SP;Berwick ZC;Kohr M;Svendsen M;Mather KJ;Tune JD
我们研究了冠状动脉内胰高血糖素样肽（GLP）-1（7-36）对正常和缺血心肌的冠状动脉血管张力、心脏收缩功能和代谢的急性剂量依赖性作用。在冠状动脉内GLP-1（7-36）输注（10 pmol/L至1 nmol/L）之前和期间，在100和40 mmHg的冠状动脉灌注压（CPP）下，在开胸麻醉犬中进行实验。还在离体冠状动脉中进行了等距张力研究。通过Western印迹和免疫组织化学分析评估GLP-1受体（GLP-1 R）的心脏和冠状动脉表达。GLP-1 R存在于心肌和冠状血管中。完整和内皮剥脱的冠状动脉环的张力不受GLP-1的影响。在正常灌注压（100 mmHg）下，冠状动脉内GLP-1（7-36）（目标血浆浓度10 pmol/L至1 nmol/L）不影响血压、冠状动脉血流量或心肌耗氧量（MVO 2）;然而，心输出量和每搏输出量适度降低。在未治疗的对照心脏中，将CPP降至40 mmHg导致冠状动脉血流量（0.50 ±0.10至0.17 ±0.03 mL/min/g; P < 0.001）和MVO 2（27 ±2.3至15 ±2.7 μL O2/min/g; P < 0.001）显著降低。在CPP = 40 mmHg时，GLP-1对冠状动脉血流量、MVO 2或局部缩短没有影响，但剂量依赖性地增加心肌葡萄糖摄取，从基线时的0.11±0.02 μmol/min/g增加到1 nmol/L GLP-1时的0.17±0.04 μmol/min/g（P < 0.001）。这些数据表明，GLP-1（7-36）的急性冠状动脉内给药优先增强缺血心肌中的葡萄糖代谢，与对心脏收缩功能或冠状动脉血流的影响无关。
We examined the acute dose-dependent effects of intracoronary glucagon-like peptide (GLP)-1 (7–36) on coronary vascular tone, cardiac contractile function and metabolism in normal and ischemic myocardium. Experiments were conducted in open chest, anesthetized dogs at coronary perfusion pressures (CPP) of 100 and 40 mmHg before and during intracoronary GLP-1 (7–36) infusion (10 pmol/L to 1 nmol/L). Isometric tension studies were also conducted in isolated coronary arteries. Cardiac and coronary expression of GLP-1 receptors (GLP-1R) was assessed by Western blot and immunohistochemical analysis. GLP-1R was present in the myocardium and the coronary vasculature. The tension of intact and endothelium-denuded coronary artery rings was unaffected by GLP-1. At normal perfusion pressure (100 mmHg), intracoronary GLP-1 (7–36) (targeting plasma concentration 10 pmol/L to 1 nmol/L) did not affect blood pressure, coronary blood flow or myocardial oxygen consumption (MVO2); however, there were modest reductions in cardiac output and stroke volume. In untreated control hearts, reducing CPP to 40 mmHg produced marked reductions in coronary blood flow (0.50 ±0.10 to 0.17 ±0.03 mL/min/g; P < 0.001) and MVO2 (27 ±2.3 to 15 ±2.7 μL O2/min/g; P < 0.001). At CPP = 40 mmHg, GLP-1 had no effect on coronary blood flow, MVO2 or regional shortening, but dose-dependently increased myocardial glucose uptake from 0.11±0.02 μmol/min/g at baseline to 0.17±0.04 μmol/min/g at 1 nmol/L GLP-1 (P < 0.001). These data indicate that acute, intracoronary administration of GLP-1 (7–36) preferentially augments glucose metabolism in ischemic myocardium, independent of effects on cardiac contractile function or coronary blood flow.
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DOI：
10.1161/circheartfailure.109.900282
发表时间：
2010-07
期刊：
Circulation. Heart failure
影响因子：
--
作者：
Bhashyam S;Fields AV;Patterson B;Testani JM;Chen L;Shen YT;Shannon RP
通讯作者：
Shannon RP
DOI：
10.1152/ajpheart.2000.278.4.h1345
发表时间：
2000-04-01
影响因子：
4.8
作者：
Korvald, C;Elvenes, OP;Myrmel, T
通讯作者：
Myrmel, T
影响因子：
3.9
作者：
Green, Brian D.;Hand, Katharine V.;Grieve, David J.
通讯作者：
Grieve, David J.
影响因子：
37.8
作者：
Nikolaidis, LA;Elahi, D;Shannon, RP
通讯作者：
Shannon, RP
影响因子：
7.7
作者：
Bose, AK;Mocanu, MM;Yellon, DM
通讯作者：
Yellon, DM