Department of Cardiac Surgery, University of Leipzig Heart Center, 04178 Leipzig, Germany.
Basic Res Cardiol. 2010 May;105(3):357-64. doi: 10.1007/s00395-010-0087-2. Epub 2010 Feb 5.
In patients, inactivity, obesity and insulin resistance are associated with increased incidence of heart failure. Rats selectively bred for low (LCR) intrinsic aerobic exercise capacity show signs of the metabolic syndrome including insulin resistance, compared to their counterparts bred for high intrinsic aerobic capacity (HCR). We reasoned that systemic insulin resistance in LCR should translate to impaired substrate oxidation and reduced insulin sensitivity in the heart. Isolated hearts were perfused in the working mode to analyze cardiac function, substrate oxidation patterns, insulin response, and oxygen consumption. After 22 generations of selective breeding, LCR displayed reduction of exercise capacity (LCR vs. HCR: distance 280 +/- 12 vs. 1,968 +/- 63 m, time 19.5 +/- 0.6 vs. 71.7 +/- 1.4 min, speed 19.2 +/- 0.3 vs. 45.3 +/- 0.7 m/min; all p < 0.05). At 21 weeks, body weight (+34%), tibia length (+6%), heart weight (+31%), and heart weight to tibia length ratio (+24%; all p < 0.05) were increased. LCR display higher random glucose, higher fasting glucose, and higher insulin levels in serum than HCR indicating the presence of insulin resistance in LCR. Here, in contrast, isolated hearts showed no differences in glucose (0.22 +/- 0.02 micromol/min/g dry) or fatty acid oxidation (0.79 +/- 0.10 micromol/min/g dry), oxygen consumption (28.3 +/- 4.1 nmol O(2)/min/g dry) or cardiac power (18.6 +/- 1.6 mW/g dry). Furthermore, sensitivity to insulin (Deltaglucose oxidation: +0.57 +/- 0.095 mumol/min/g dry) was not different between the two populations. Low intrinsic exercise capacity and systemic insulin resistance in rats are not associated with changes in cardiac substrate oxidation, insulin sensitivity, oxygen consumption, or cardiac function. The lack of cardiac insulin resistance in the face of systemic insulin resistance supports a concept of different pathomechanisms for these two conditions.
在患者中，不活动、肥胖和胰岛素抵抗与心力衰竭发生率的增加有关。与高内在有氧能力（HCR）相比，选择性繁殖的低（LCR）内在有氧运动能力的大鼠表现出代谢综合征的迹象，包括胰岛素抵抗。我们推测，LCR 中的系统性胰岛素抵抗应该转化为心脏中底物氧化受损和胰岛素敏感性降低。分离的心脏在工作模式下进行灌注，以分析心脏功能、底物氧化模式、胰岛素反应和耗氧量。经过 22 代的选择性繁殖，LCR 显示运动能力降低（LCR 与 HCR：距离 280 +/- 12 与 1968 +/- 63 m，时间 19.5 +/- 0.6 与 71.7 +/- 1.4 分钟，速度 19.2 +/- 0.3 与 45.3 +/- 0.7 m/min；所有 p < 0.05）。在 21 周时，体重（增加 34%）、胫骨长度（增加 6%）、心脏重量（增加 31%）和心脏重量与胫骨长度比（增加 24%；所有 p < 0.05）增加。LCR 血清中的随机血糖、空腹血糖和胰岛素水平均高于 HCR，表明 LCR 存在胰岛素抵抗。与此相反，分离的心脏在葡萄糖（0.22 +/- 0.02 微摩尔/分钟/克干）或脂肪酸氧化（0.79 +/- 0.10 微摩尔/分钟/克干）、耗氧量（28.3 +/- 4.1 毫摩尔 O（2）/分钟/克干）或心脏功率（18.6 +/- 1.6 毫瓦/克干）方面没有差异。此外，两人群之间对胰岛素的敏感性（葡萄糖氧化增加：+0.57 +/- 0.095 微摩尔/分钟/克干）没有差异。大鼠内在运动能力低和系统性胰岛素抵抗与心脏底物氧化、胰岛素敏感性、耗氧量或心脏功能的变化无关。在系统性胰岛素抵抗的情况下，心脏缺乏胰岛素抵抗支持这两种情况存在不同发病机制的概念。
