Cardiac Metabolism Research Group, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
J Mol Cell Cardiol. 2011 Apr;50(4):598-605. doi: 10.1016/j.yjmcc.2011.01.007. Epub 2011 Jan 22.
The diabetic heart becomes metabolically remodelled as a consequence of exposure to abnormal circulating substrates and hormones. Fatty acid uptake and metabolism are increased in the type 2 diabetic heart, resulting in accumulation of intracellular lipid intermediates and an increased contribution of fatty acids towards energy generation. Cardiac glucose uptake and oxidation are decreased, predominantly due to increased fatty acid metabolism, which suppresses glucose utilisation via the Randle cycle. These metabolic changes decrease cardiac efficiency and energetics in both humans and animal models of diabetes. Diabetic hearts have decreased recovery following ischemia, indicating a reduced tolerance to oxygen-limited conditions. There is evidence that diabetic hearts have a compromised hypoxia signalling pathway, as hypoxia-inducible factor (HIF) and downstream signalling from HIF are reduced following ischemia. Failure to activate HIF under oxygen-limited conditions results in less angiogenesis, and an inability to upregulate glycolytic ATP generation. Given that glycolysis is already suppressed in the diabetic heart under normoxic conditions, the inability to upregulate glycolysis in response to hypoxia may have deleterious effects on ATP production. Thus, impaired HIF signalling may contribute to metabolic and energetic abnormalities, and impaired collateral vessel development following myocardial infarction in the type 2 diabetic heart.
糖尿病心脏由于暴露于异常循环底物和激素而发生代谢重塑。2 型糖尿病心脏中脂肪酸的摄取和代谢增加，导致细胞内脂质中间体的积累和脂肪酸对能量生成的贡献增加。心脏葡萄糖摄取和氧化减少，主要是由于脂肪酸代谢增加，通过 Randle 循环抑制葡萄糖利用。这些代谢变化降低了糖尿病患者和动物模型的心脏效率和能量。糖尿病心脏在缺血后恢复能力下降，表明对缺氧条件的耐受性降低。有证据表明，糖尿病心脏的缺氧信号通路受损，因为缺血后缺氧诱导因子 (HIF) 和 HIF 的下游信号减少。在缺氧条件下未能激活 HIF 会导致血管生成减少，以及无法上调糖酵解 ATP 生成。鉴于在正常氧条件下糖尿病心脏已经抑制了糖酵解，因此无法对缺氧做出反应而上调糖酵解可能对 ATP 产生有害影响。因此，HIF 信号转导受损可能导致代谢和能量异常，并导致 2 型糖尿病心脏梗死后侧支血管发育受损。
