胰岛素对胰岛素依赖型糖尿病患者骨骼肌血流和血容量的影响：使用[15O]H2O、[15O]CO和正电子发射断层扫描的研究

Effects of insulin on blood flow and volume in skeletal muscle of patients with IDDM: studies using [15O]H2O, [15O]CO, and positron emission tomography.

作者信息

Raitakari M, Nuutila P, Knuuti J, Raitakari O T, Laine H, Ruotsalainen U, Kirvelä O, Takala T O, Iida H, Yki-Järvinen H

机构信息

Turku Positron Emission Tomography Center, Department of Anesthesiology, University of Turku, Finland.

出版信息

Diabetes. 1997 Dec;46(12):2017-21. doi: 10.2337/diab.46.12.2017.

DOI:10.2337/diab.46.12.2017

PMID:9392489

Abstract

Exaggerated vasoconstriction and blunted vasodilation of peripheral resistance arteries to various vasoactive agents characterize patients with IDDM. We characterized the hemodynamic effects of insulin in skeletal muscle in patients with IDDM. Muscle blood flow and blood volume were measured basally and during a high-dose insulin infusion (5 mU x kg(-1) x min[-1]) in seven normotensive patients with IDDM (age, 30 +/- 6 years; BMI, 24.5 +/- 2.0 kg/m2; blood pressure, 124 +/- 12/78 +/- 11 mmHg) and nine matched normal subjects, using [15O]H2O, [15O]CO, and positron emission tomography (PET). Whole-body insulin sensitivity was determined using the euglycemic insulin clamp technique. Insulin-stimulated whole-body glucose uptake was significantly lower in the patients with IDDM (45 +/- 15 micromol x kg(-1) x min[-1]) than in the normal subjects (62 +/- 14 micromol x kg(-1) x min[-1]) (P < 0.05). Insulin increased muscle blood flow by 111 +/- 69% above basal from 3.0 +/- 2.0 to 5.8 +/- 3.0 ml x 100 g(-1) muscle x min(-1) (P < 0.005) in the normal subjects, but only by 42 +/- 30% from 2.0 +/- 0.9 to 2.9 +/- 1.4 ml x 100 g(-1) muscle x min(-1) (P < 0.005) in patients with IDDM (P < 0.05 for change in flow in IDDM vs. normal subjects). The calculated muscle vascular resistances were comparable basally, but higher during hyperinsulinemia in the patients with IDDM (37 +/- 17 mmHg x 100 g x min x ml[-1]) than in the normal subjects (16 +/- 7 mmHg x 100 g x min x ml[-l]) (P < 0.05). Muscle blood volume increased significantly by insulin in both groups without any difference between the groups. We conclude that the ability of supraphysiological concentrations of insulin to stimulate muscle blood flow is blunted in patients with IDDM, because of the inability of insulin to stimulate linear flow velocity rather than blood volume in skeletal muscle. This defect adds yet another defect to the list of abnormalities in vascular function in IDDM, which might predispose these patients to develop hypertension.

摘要

胰岛素依赖型糖尿病（IDDM）患者的外周阻力动脉对各种血管活性物质存在血管收缩过度和血管舒张减弱的情况。我们对IDDM患者骨骼肌中胰岛素的血流动力学效应进行了研究。在7名血压正常的IDDM患者（年龄30±6岁；体重指数24.5±2.0kg/m²；血压124±12/78±11mmHg）和9名匹配的正常受试者中，使用[15O]H2O、[15O]CO和正电子发射断层扫描（PET），在基础状态及高剂量胰岛素输注（5mU·kg⁻¹·min⁻¹）期间测量肌肉血流量和血容量。采用正常血糖胰岛素钳夹技术测定全身胰岛素敏感性。IDDM患者胰岛素刺激的全身葡萄糖摄取量（45±15μmol·kg⁻¹·min⁻¹）显著低于正常受试者（62±14μmol·kg⁻¹·min⁻¹）（P<0.05）。在正常受试者中，胰岛素使肌肉血流量比基础值增加111±69%，从3.0±2.0ml·100g⁻¹肌肉·min⁻¹增至5.8±3.0ml·100g⁻¹肌肉·min⁻¹（P<0.005），而在IDDM患者中仅增加42±30%，从2.0±0.9ml·100g⁻¹肌肉·min⁻¹增至2.9±1.4ml·100g⁻¹肌肉·min⁻¹（P<0.005）（IDDM患者与正常受试者血流变化的P<0.05）。计算得出的肌肉血管阻力在基础状态时相当，但在IDDM患者高胰岛素血症期间（37±17mmHg·100g·min·ml⁻¹）高于正常受试者（16±7mmHg·100g·min·ml⁻¹）（P<0.05）。两组中胰岛素均使肌肉血容量显著增加，且两组间无差异。我们得出结论，IDDM患者中，超生理浓度胰岛素刺激肌肉血流的能力减弱，原因是胰岛素无法刺激骨骼肌中的线性血流速度而非血容量。这一缺陷为IDDM血管功能异常清单增添了又一异常情况，可能使这些患者易患高血压。