GLUT4在调控骨骼肌葡萄糖转运中的作用研究进展

葡萄糖作为运动骨骼肌收缩的重要能量来源,对机体代谢稳态的维持具有重要作用。葡萄糖通过葡萄糖转运蛋白4(glucose transporter 4,GLUT4)易化扩散进入骨骼肌细胞进而实现葡萄糖的转运和摄取。在运动、胰岛素和AICAR(5-Aminoimidazole-4-carboxamide-1-β-D-ribofuranoside)等作用下,GLUT4能够从骨骼肌细胞内储存库转位到细胞膜和T管上。尽管目前很多研究证实了运动、胰岛素以及AICAR等因素都能够调节骨骼肌细胞的GLUT4转位,为进一步了解骨骼肌葡萄糖转运和摄取的分子机制提供了理论基础,然而当前关于调控GLUT4转位的机制还尚未有定论。因而本文通过综述目前国内外对于不同因素下GLUT4介导骨骼肌葡萄糖摄取的调控机制研究,分析GLUT4在运动调控骨骼肌葡萄糖转运过程中的作用,以期为揭示运动防治代谢性疾病的机制研究提供理论依据。     

心肌细胞葡萄糖转运蛋白4的转运调控及与心肌活力关系的研究进展

葡萄糖是心肌能量代谢的主要底物之一,在心肌缺血时是心肌的主要能量来源。葡萄糖通过细胞膜进入细胞内是心肌细胞葡萄糖代谢的第一步,也是心肌细胞利用葡萄糖的主要限速步骤。葡萄糖是依靠细胞膜上的葡萄糖转运蛋白（GLUTs）而进入细胞内的,GLUT4是心肌细胞主要的葡萄糖转运载体。GLUT4的质和量对心肌葡萄糖的跨膜转运起着决定性作用。因此,明确心肌葡萄糖转运及心肌细胞GLUT4的基因表达调控机制、转位调控机制、内在活性调控机制,对临床诊断心肌能量代谢性疾病具有重要意义。该文对近年来有关心肌葡萄糖转运及GLUT4调控方面的研究进行综述。     

运动促进大鼠骨骼肌细胞葡萄糖运载体4的转位

目的 :研究运动对SD大鼠骨骼肌细胞葡萄糖运载体 4 (GLUT4 )转位机制的影响。方法 :将SD大鼠随机分为 2组 :对照组和运动组。运动组大鼠进行 6周游泳训练。以Western印迹法对 2组大鼠骨骼肌细胞内膜和外膜的GLUT4含量进行检测 ,同时实验前后检测大鼠血清胰岛素和血糖浓度。结果 :运动组大鼠经过 6周游泳训练 ,与对照组大鼠相比 ,骨骼肌细胞内膜GLUT4含量增加 16 0 % (P <0 0 1) ,细胞外膜GLUT4含量增加 71 9% (P <0 0 1)。结论 :运动可促进骨骼肌细胞内膜GLUT4向细胞外膜转位 ,从而提高肌细胞对葡萄糖的摄取和利用。     

颅脑创伤应激对外周组织胰岛素敏感性的影响

各种类型创伤、手术应激中均普遍存在外周组织（骨骼肌和皮下脂肪组织）一过性的胰岛素敏感性下降现象。已有研究提示该现象与外周组织葡萄糖转运蛋白4（glucose transporter-4，GLUT4）介导的糖转运体系效能下降有关。但目前研究仅涉及GLUT4的转位功能障碍方面，在GLUT4的基因表达层面所知甚少。笔者通过RT—PCR法测定颅脑损伤大鼠骨骼肌和皮下脂肪组织GLUT4 mRNA的表达来探讨颅脑创伤应激对胰岛素敏感性的影响及其内在机制。     

游离脂肪酸可抑制大鼠骨骼肌对葡萄糖的摄取和利用

目的：观察游离脂肪酸对大鼠骨骼肌葡萄糖转运蛋白4（GLUT4）基因及蛋白表达的影响。方法：分离、培养新生Sprague-Dawley大鼠骨骼肌细胞,分别与软脂酸（0．25mmol/L)或油酸（0．125mmol/L)孵育12、24、36h,提取蛋白后用Western印迹法检测葡萄糖转运蛋白4（GTUT4）的蛋白水平;用斑点和印迹杂交法检测骨骼肌细胞内GLUT4 RNA含量的变化。结果：经软脂酸和油酸孵育12、24、36h后骨骼肌细胞GLUT4的蛋白和RNA水平均显著降低（P＜0．05）。结论：游离脂肪酸可抑制葡萄糖转运蛋白4的基因及蛋白表达。     

TBC1D1/4在有氧运动促进骨骼肌细胞葡萄糖转运中的作用

TBC1D1(Tre-2/BUB2/cdc1 domain family 1)和TBC1D4(又名Akt Substrate of 160 k Da,AS160)均为骨骼肌细胞内的GTP酶激活蛋白(Rab-GTPase activating proteins,Rab-GAP),参与骨骼肌细胞葡萄糖转运蛋白4(GLUT4)在细胞内的转位过程,调节骨骼肌细胞葡萄糖转运。最新研究表明,TBC1D1和TBC1D4在有氧运动促进骨骼肌细胞葡萄糖转运过程中发挥重要作用,骨骼肌细胞胰岛素信号通路活性下降引起GLUT4转位异常、导致骨骼肌细胞葡萄糖转运能力下降。有氧运动能够显著改善机体能量代谢水平,已被广泛应用于临床肥胖、胰岛素抵抗、2型糖尿病等代谢性疾病的治疗。本文综述TBC1D1和TBC1D4在有氧运动促进骨骼肌细胞葡萄糖转运中的作用,以期为运动防治代谢性疾病的机制研究提供理论依据。     

18F-FDG PET/CT心肌“缺血记忆”显像的实验研究

目的 通过犬18F-FDG PET/CT动态显像探讨缺血心肌葡萄糖代谢改变(也称“缺血记忆”)和缺血程度的关系.方法 将8条杂种犬用随机抽签法分为球囊封堵20 min组(4条)和40 min组(4条),所有犬均行基础、缺血-再灌注1h和24 h的18F-FDG PET/CT动态心肌代谢显像(禁食12h以上),以及99Tcm-MIBI SPECT心肌灌注显像.利用葡萄糖摄取定量分析软件(Carimas Core)计算冠状动脉封堵区和非缺血区心肌的葡萄糖摄取率k(k缺血和k非缺血),获得两者比值K(K=k缺血/k非缺血).在3次PET/CT显像同期分别进行心脏超声检查,评价室壁运动情况.所有显像完成后处死犬,分别取缺血区、非缺血区心肌组织行组织病理学检查.同一实验组前后比较采用配对t检验,其他采用非参数检验分析.结果 2组犬基础心肌灌注显像未见异常,预封堵区心肌/非缺血区心肌18F-FDG摄取率比值K差异无统计学意义(1.02 ±0.06与1.03±0.05,Z=-0.29,P＞0.05),室壁运动正常.缺血-再灌注1h后2组心肌灌注显像亦未见异常,但缺血区18F-FDG摄取增加,40 min组的K值高于20 min组(2.31±0.13与1.87 ±0.09,Z=-2.31,P＜0.05),缺血心肌出现不同程度的室壁运动减弱.缺血-再灌注24h后2组心肌灌注显像未见异常,但40 min组的K值仍稍高于基础状态(1.15±0.02与1.03 ±0.05,=4.32,P＜0.05),而20 min组的K值与基础状态比较差异无统计学意义(1.05±0.04与1.02±0.06,=0.87,P＞0.05),2组室壁运动均未见异常.心肌组织检查示2组缺血部位心肌细胞排列整齐,心肌细胞间质无水肿出血,未见心肌细胞肌浆凝集或肌溶性破坏,也未见炎性反应.结论 心肌“缺血记忆”与缺血程度相关.18F-FDG PET/CT心肌“缺血记忆”显像可能在急性冠状动脉综合征患者的诊断、治疗方面具有重要应用价值.     

18F-氟脱氧葡萄糖符合线路诊断心肌梗死后的心肌活力

目的利用^18F-氟脱氧葡萄糖（^18F-FDG）符合线路空腹，糖负荷代谢显像和^99mTc-甲氧基异丁基异腈（^99mTc-MIBI）来判断心肌梗死后心肌的活力。方法24例心肌梗死患者进行血管造影、^99mTc-MIBI负荷和（或）静息血流灌注检查、^18F-FDG符合线路心肌代谢显像（空腹-葡萄糖负荷显像一日法）。结果^99mTc-MIBI灌注显像发现的27个缺血节段在空腹和糖负荷均有^18F-FDG的摄取，心肌存活；22个缺血节段在空腹和糖负荷显像后没有^18F-FDG的摄取，心肌没有活力。空腹状态心肌对^18F-FDG摄取较少，有活力的心肌缺血节段显示特别清晰，图像质量较差；葡萄糖负荷后活力心肌摄取^18F-FDG，图像质量有明显改善。结论空腹和糖负荷都可判断心肌活力，空腹显像时图像的质量稍差，糖负荷能够提高图像质量。     

肿瘤患者心肌摄取18F-FDG程度与血糖水平的关系

目的研究血糖水平对心肌摄取18F-氟脱氧葡萄糖的影响.方法在406例符合探测检查的肿瘤患者中,选取心脏在显像范围内,且临床资料完整的141名患者.进行18F-氟脱氧葡萄糖肿瘤检测,分析心肌影像质量的分析,对比研究心肌摄取18F-氟脱氧葡萄糖的程度和血糖水平的关系.结果141例肿瘤检测患者心肌摄取18F-氟脱氧葡萄糖的程度与血糖水平无相关性(P＞0.05).结论肿瘤患者的心肌对18F-氟脱氧葡萄糖的摄取程度可能受血糖水平以外的其他因素影响,因此检查前血糖水平不能预测心肌显影的质量.     

过度训练对大鼠骨骼肌糖原含量、AMPK活性及肌膜GLUT4的影响

目的:观察过度训练后大鼠骨骼肌糖原含量、AMPK活性和肌膜GLUT4蛋白含量的变化,探讨过度训练与骨骼肌葡萄糖代谢之间的联系。方法:27只SD大鼠随机分为安静对照组(A组),大强度运动组(B组)和过度训练组(C组)。B、C组进行9周大强度耐力训练,其中B组每天训练60分钟,C组每天训练120分钟,每周训练6天。9周后分别测定各组大鼠腓肠肌糖原、AMPK活性和肌膜GLUT4含量。结果:与A组比较,B组肌膜GLUT4升高,AMPK活性显著提高,肌糖原含量有上升趋势;C组肌膜GLUT4明显低于B组,AMPK活性受到抑制,但肌糖原含量正常。结论:过度训练状态下,大鼠肌肉AMPK活性降低,GLUT4蛋白向肌膜转位受抑,可能影响肌膜葡萄糖的转运。本实验结果不支持过度训练的糖原耗竭学说。     

Muscle insulin resistance amended with exercise training: role of GLUT4 expression

PURPOSE: Muscle insulin resistance is characterized by the inability of a normal insulin concentration to produce a favorable rate of glucose uptake. The muscle of the obese Zucker rat is highly insulin resistant. The purpose of this review is to discuss the cellular defects associated with the muscle insulin resistance of the obese Zucker rat, as well as the mechanisms by which exercise training alleviates or compensates for these defects. Emphasis will be given to the importance of an increased GLUT4 expression on alleviating muscle insulin resistance. METHODS: A review of the relative research from my laboratory and the scientific literature was performed to obtain information on the muscle insulin resistance of the obese Zucker rat and its response to exercise training. RESULTS: The insulin resistance of the obese Zucker rat results from defects in the insulin signaling cascade, which limits translocation of the glucose transporter GLUT4 to the plasma membrane upon insulin binding to its receptor. Exercise training improves the muscle insulin resistance of obese Zucker rat but does not correct the defects in insulin signaling or GLUT4 translocation. The improvement in insulin resistance, i.e., glucose transport, is correlated with an increased expression of GLUT4 protein. Preventing GLUT4 overexpression during exercise training will inhibit the improvement in insulin-stimulated glucose transport. CONCLUSION: Exercise training does not correct but compensates for the defects in muscle insulin resistance by increasing expression of GLUT4. This increase in GLUT4 protein is essential for the improvement in muscle insulin resistance.     

Exercise and insulin sensitivity: a review

Physical activity has a beneficial effect on insulin sensitivity in normal as well as insulin resistant populations. A distinction should be made between the acute effects of exercise and genuine training effects. Up to two hours after exercise, glucose uptake is in part elevated due to insulin independent mechanisms, probably involving a contraction-induced increase in the amount of GLUT4 associated with the plasma membrane and T-tubules. However, a single bout of exercise can increase insulin sensitivity for at least 16 h post exercise in healthy as well as NIDDM subjects. Recent studies have accordingly shown that acute exercise also enhances insulin stimulated GLUT4 translocation. Increases in muscle GLUT4 protein content contribute to this effect, and in addition it has been hypothesized that the depletion of muscle glycogen stores with exercise plays a role herein. Physical training potentiates the effect of exercise on insulin sensitivity through multiple adaptations in glucose transport and metabolism. In addition, training may elicit favourable changes in lipid metabolism and can bring about improvements in the regulation of hepatic glucose output, which is especially relevant to NIDDM. It is concluded that physical training can be considered to play an important, if not essential role in the treatment and prevention of insulin insensitivity.     

Skeletal muscle pathways of contraction-enhanced glucose uptake

Muscle contraction acutely increases glucose transport in both healthy and type 2 diabetic individuals. Since glucose uptake during muscle contraction has been observed in the absence of insulin, the existence of an insulin-independent pathway has been suggested to explain this phenomenon. However, the exact mechanism behind the translocation of GLUT4 vesicles through the sarcolemma during muscle contraction is still unknown. Some substances, such as AMPK and calcium activated proteins, have been suggested as potential mediators but the exact mechanisms of their involvement remain to be elucidated. A hypothetical convergence point between the insulin cascade and the potential pathways triggered by muscle contraction has been suggested. Therefore, the earliest concept that two different routes exist in skeletal muscle has been progressively modified to the notion that glucose uptake is induced by muscle contraction via components of the insulin pathway. With further consideration, increased glucose uptake and enhanced insulin sensitivity observed during/after exercise might be explained by a metabolic- and calcium-dependent activation of several intermediate molecules of the insulin cascade. This paper aimed to review the literature in order to examine in detail these concepts behind muscle contraction-induced glucose uptake.     

Sending the signal: molecular mechanisms regulating glucose uptake

The molecular signaling mechanisms by which insulin leads to increased glucose transport and metabolism and gene expression are not completely elucidated. We have characterized the nature of insulin signaling defects in skeletal muscle from Type 2 diabetic patients. Insulin receptor substrate (IRS-1) phosphorylation, phosphatidylinositol (PI) 3-kinase activity, and glucose transport activity are impaired as a consequence of functional defects, whereas insulin receptor tyrosine phosphorylation, mitogen-activated protein kinase (MAPK) phosphorylation, and glycogen synthase activity are normal. Using biotinylated photoaffinity labeling, we have shown that reduced cell surface GLUT4 levels can explain glucose transport defects in skeletal muscle from Type 2 diabetic patients under insulin-stimulated conditions. Current work is focused on mechanisms behind insulin-dependent and insulin-independent regulation of glucose uptake. We have recently determined the independent effects of insulin and hypoxia/AICAR exposure on glucose transport and cell surface GLUT4 content in skeletal muscle from nondiabetic and Type 2 diabetic subjects. Hypoxia and AICAR increase glucose transport via an insulin-independent mechanism involving activation of 5'-AMP-activated kinase (AMPK). AMPK signaling is intact, because 5-aminoimidazole-4-carboxamide 1-beta-D-ribonucleoside (AICAR) increased AMPK and acetyl-CoA carboxylase (ACC) phosphorylation to a similar extent in Type 2 diabetic and nondiabetic subjects. However, AICAR responses on glucose uptake were impaired. Our studies highlight important AMPK-dependent and independent pathways in the regulation of GLUT4 and glucose transport activity in insulin resistant skeletal muscle. Understanding signaling mechanisms to downstream metabolic responses may provide valuable clues to a future therapy for Type 2 diabetes.     

GIK对急性缺血/再灌注犬心肌损伤的影响

目的比较GIK（葡萄糖-胰岛素-钾）和GK（葡萄糖-钾）对犬在体急性心肌缺血/再灌注（MI/R）血液流变性和心肌损伤的影响,讨论胰岛素在GIK保护心肌缺血中的作用。方法采用定量缺血的方法制备犬急性MI/R模型,再灌注GIK、GK或生理盐水4 h后,抽取冠状静脉窦血,比较各组的红细胞压积（HCT）、全血高切粘度（ηbh）、全血低切粘度（ηbl）、血浆乳酸脱氢酶（LDH）、肌酸激酶CK）和梗死区面积的变化。结果 GIK组与另两组相比,再灌注后ηbh、ηbl、TK、HCT均有明显的改变（P〈0.05）。GIK明显降低心肌梗死后LDH和CK活性（P〈0.05）,心肌梗死范围减少（P〈0.05）。结论 GIK可改善MI/R犬血液流变学特性,降低全血黏度;减轻心肌损伤,显著地缩小急性心肌梗死范围,并减轻梗死程度,胰岛素是GIK中的关键成分。     

Myocardial glucose uptake after dobutamine stress in chronic hibernating swine myocardium

BACKGROUND: In patients with hibernating myocardium, regional uptake of the glucose analog 2-fluorine 18-fluoro-2-deoxy-d-glucose (FDG) is increased under resting conditions. It is unclear whether the degree of increased FDG uptake correlates with the degree of impaired blood flow response and whether chronic changes in the glucose transporters may play a role in the enhanced FDG uptake under fasted conditions. METHODS AND RESULTS: Twelve swine were instrumented with a constrictor on the left anterior descending (LAD) artery. Serial echocardiography and positron emission tomography studies were done to assess temporal changes in myocardial function, blood flow, and FDG uptake. One week after surgery (early study), wall thickening, blood flow, and postdobutamine FDG uptake in LAD and remote territories were similar. By approximately 6 weeks (late study), baseline wall thickening in the LAD region was lower than in remote regions (20% +/- 7% and 36% +/- 6%, P <.05), as was dobutamine-stimulated blood flow (0.92 +/- 0.16 mL. min(-1). g(-1) and 1.17 +/- 0.20 mL. min(-1). g(-1) in LAD and remote regions, respectively; P <.05). After the dobutamine infusion, FDG uptake in the LAD region during fasted conditions was higher than in remote regions (0.128 +/- 0.053 micromol. min(-1). g(-1) and 0.098 +/- 0.044 micromol. min(-1). g(-1), respectively; P <.05), and the increase was proportional to the impairment in dobutamine blood flow (r(2) = 0.62, P <.001). After the animals were killed, the LAD region showed a higher content of GLUT4 by immunoblots and a greater degree of translocation as estimated by immunohistochemistry. In 5 additional hibernating pigs studied under resting fasted conditions, FDG uptake and GLUT4 translocation were also higher in the LAD region, in the absence of dobutamine stimulation. CONCLUSIONS: In hibernating myocardium, regional FDG uptake under fasting conditions is higher than in remote regions, both at rest and after an infusion of dobutamine. The degree of poststress FDG uptake is proportional to the impaired stress-induced blood flow. Total GLUT4 content as well as membrane-bound protein is higher in the hibernating tissue, and these changes may facilitate the observed increase in FDG uptake.     

Experimental study on “ischemic memory” of myocardium with different ischemic degrees by 18 F-FDG PET/CT

Glucose metabolism and ranges of ischemic cardiomyocytes in model rats under fasting or feeding were compared by 18F-FDG PET/CT, respectively, to investigate the changes of glucose metabolism after myocardial reperfusion, and to determine time window of myocardial “ischemic memory” under feeding. The ischemic–reperfusion model rats were established by ligating the left anterior descending coronary artery of rats. In fasting–feeding experiment, long-ischemia rats (n = 10) under fasting or feeding were subjected to 18F-FDG PET/CT at 24 h after modeling. Ischemic myocardium range and glucose metabolism were compared by calculating volume of interest (VOI), and mean standard uptake value (SUVmean). Under feeding, model rats in short, intermediate and long-ischemia groups were subjected to 18F-FDG PET/CT at 24, 48, and 72 h and long-ischemia rats were also subjected to 18F-FDG PET/CT at 96 h, and VOI and SUVmean were calculated and compared. (1) Under fasting, myocardial ischemic area of model rats showed “focal” 18F-FDG uptake, while “focal” 18F-FDG uptake defect appeared in the same area of myocardium under feeding and the difference was not statistically significant (P > 0.05). (2) Under feeding, PET myocardial images of model rats in three groups at 24 h and 48 h showed that there was an 18F-FDG uptake defect area near the apex of left ventricular wall. The images at 72 h showed that there was no abnormal 18F-FDG uptake defect area in short and intermediate-ischemia groups, while 18F-FDG uptake defect area in long-ischemia group disappeared at 96 h. Variance analysis of repeated measures was performed for data of three groups, which showed there was statistical significance between myocardial ischemia degree and “ischemic memory” time window (P < 0.05), and also between myocardial ischemia degree and difference of myocardial defect volume (P < 0.05). Under feeding, recent myocardial ischemia could be diagnosed by 18F-FDG PET/CT. Under feeding, “ischemic memory” time window for short and intermediate-myocardial ischemia was at least 48 h and for long ischemia was at least 72 h. This study suggested that as the degree of myocardial ischemia increased, “ischemic memory” time window also extended.     

Variability of insulin-stimulated myocardial glucose uptake in healthy elderly subjects

The aim of this study was to assess regional and global variability of insulin-stimulated myocardial glucose uptake in healthy elderly subjects and to evaluate potentially responsible factors. Twenty men with a mean age of 64 years, no history of cardiovascular disease, and normal blood pressure, bicycle exercise test, electrocardiogram and echocardiography were studied [ P(coronary artery disease) <5%]. Whole-body insulin sensitivity and insulin-stimulated myocardial glucose uptake were measured during hyperinsulinaemic euglycaemic glucose clamp with fluorine-18 fluorodeoxyglucose, and myocardial rest and hyperaemic blood flow during dipyridamole infusion were measured with nitrogen-13 ammonia and positron emission tomography in 16 left ventricular myocardial segments. Intra-individual and inter-individual variability of insulin-stimulated myocardial glucose uptake [relative dispersion = (standard deviation/mean)] was 13% and 29% respectively. Although inter-individual variability of glucose uptake and blood flow at rest was of the same magnitude, no correlation was found between these measures. Regional and global insulin-stimulated myocardial glucose uptake correlated linearly with whole-body insulin sensitivity ( r=0.51, P<0.05 and r=0.56, P<0.01). The strongest independent association by multivariate linear regression analysis was found between myocardial glucose uptake and hyperaemic blood flow ( r=0.63, P<0.005). We conclude that in healthy elderly subjects, insulin-stimulated myocardial glucose uptake is homogeneous throughout the left ventricle, but has moderate inter-individual variability. Inter-individual variability of insulin-stimulated myocardial glucose uptake is primarily explained by variability in coronary vascular reactivity and tissue insulin sensitivity.     

Dipyridamole-induced increased glucose uptake in patients with single-vessel coronary artery disease assessed with PET

BACKGROUND: The aim of this study was to determine the relationship between vasodilatation-induced ischemia and poststress glucose uptake. Coronary vasodilators may induce myocardial ischemia due to coronary steal through collateral circulation or transmural blood flow redistribution with diminished subendocardial perfusion. Myocardial ischemia can be demonstrated by increased glucose uptake as previously shown in patients with exercise-induced ischemia. METHODS AND RESULTS: We studied 11 patients with single-vessel disease and no history of myocardial infarction. Five patients had no collateral circulation, and 6 had angiographic evidence of collateral vessels. We measured myocardial blood flow (MBF) and glucose uptake at baseline and after the administration of dipyridamole (0.56 mg/kg) with positron emission tomography, using O-15 water and fluorine 18 deoxyglucose (FDG) as perfusion and glucose tracers. MBF at baseline was 0.82 +/- 0.13 mL/g/min in normal areas and 0.80 +/- 0.15 mL/g/min in areas supplied by stenotic arteries. MBF during dipyridamole was 2.05 +/- 0.66 and 1.19 +/- 0.66 mL/g/min in normal areas and areas with stenotic arteries, respectively (P < or = .001). FDG uptake at baseline was 1.36 +/- 0.55 in normal areas and 1.57 +/- 0.62 in areas supplied by stenotic arteries. FDG uptake after dipyridamole infusion was 1.79 +/- 1.1 and 4.04 +/- 0.84 in normal areas and areas with stenotic arteries, respectively (P < or =.001). MBF and FDG uptake were not different between patients with collateral circulation and those without collateral circulation. CONCLUSIONS: Increased myocardial glucose uptake was consistently observed after dipyridamole administration in those areas with diminished coronary vasodilatory capacity. The similar MBF and FDG findings in patients with and without collateral circulation may indicate that transmural blood flow redistribution appears to be a possible mechanism of dipyridamole-induced myocardial ischemia.