Internal Medicine III, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan.
Int J Mol Sci. 2019 Jul 20;20(14):3552. doi: 10.3390/ijms20143552.
Heart failure (HF) frequently coexists with conditions associated with glucose insufficiency, such as insulin resistance and type 2 diabetes mellitus (T2DM), and patients with T2DM have a significantly high incidence of HF. These two closely related diseases cannot be separated on the basis of their treatment. Some antidiabetic drugs failed to improve cardiac outcomes in T2DM patients, despite lowering glucose levels sufficiently. This may be, at least in part, due to a lack of understanding of cardiac insulin resistance. Basic investigations have revealed the significant contribution of cardiac insulin resistance to the pathogenesis and progression of HF; however, there is no clinical evidence of the definition or treatment of cardiac insulin resistance. Mitochondrial dynamics play an important role in cardiac insulin resistance and HF because they maintain cellular homeostasis through energy production, cell survival, and cell proliferation. The innovation of diagnostic tools and/or treatment targeting mitochondrial dynamics is assumed to improve not only the insulin sensitivity of the myocardium and cardiac metabolism, but also the cardiac contraction function. In this review, we summarized the current knowledge on the correlation between cardiac insulin resistance and progression of HF, and discussed the role of mitochondrial dynamics on the pathogenesis of cardiac insulin resistance and HF. We further discuss the possibility of mitochondria-targeted intervention to improve cardiac metabolism and HF.
心力衰竭（HF）常与葡萄糖不足相关的疾病共存，如胰岛素抵抗和 2 型糖尿病（T2DM），而 T2DM 患者 HF 的发生率显著较高。这两种密切相关的疾病在治疗上不能分开。一些降糖药物尽管能充分降低血糖水平，但未能改善 T2DM 患者的心脏结局。这可能至少部分是由于对心脏胰岛素抵抗缺乏了解。基础研究揭示了心脏胰岛素抵抗对 HF 的发病机制和进展的重要贡献；然而，目前还没有关于心脏胰岛素抵抗的定义或治疗的临床证据。线粒体动力学在心脏胰岛素抵抗和 HF 中起着重要作用，因为它们通过能量产生、细胞存活和细胞增殖来维持细胞内稳态。诊断工具的创新和/或针对线粒体动力学的治疗方法的创新被认为不仅可以改善心肌和心脏代谢的胰岛素敏感性，还可以改善心脏收缩功能。在这篇综述中，我们总结了目前关于心脏胰岛素抵抗与 HF 进展之间相关性的知识，并讨论了线粒体动力学在心脏胰岛素抵抗和 HF 发病机制中的作用。我们进一步探讨了靶向线粒体干预以改善心脏代谢和 HF 的可能性。
