Oxidative Stress and Free Radical Biology Laboratory, Department of Physiology, University of Calcutta, University College of Science, Technology and Agriculture, 92 APC Road, Kolkata 700 009, India.
Oxidative Stress and Free Radical Biology Laboratory, Department of Physiology, University of Calcutta, University College of Science, Technology and Agriculture, 92 APC Road, Kolkata 700 009, India.
Life Sci. 2024 Oct 15;355:122993. doi: 10.1016/j.lfs.2024.122993. Epub 2024 Aug 16.
Addressing insulin resistance or hyperinsulinemia might offer a viable treatment approach to stop the onset of diabetic cardiomyopathy, as these conditions independently predispose to the development of the disease, which is initially characterized by diastolic abnormalities. The development of diabetic cardiomyopathy appears to be driven mainly by insulin resistance or impaired insulin signalling and/or hyperinsulinemia. Oxidative stress, hypertrophy, fibrosis, cardiac diastolic dysfunction, and, ultimately, systolic heart failure are the outcomes of these pathophysiological alterations. Melatonin is a ubiquitous indoleamine, a widely distributed compound secreted mainly by the pineal gland, and serves a variety of purposes in almost every living creature. Melatonin is found to play a leading role by improving myocardial cell metabolism, decreasing vascular endothelial cell death, reversing micro-circulation disorders, reducing myocardial fibrosis, decreasing oxidative and endoplasmic reticulum stress, regulating cell autophagy and apoptosis, and enhancing mitochondrial function. This review highlights a relationship between insulin resistance and associated cardiomyopathy. It explores the potential therapeutic strategies offered by the neurohormone melatonin, an important antioxidant that plays a leading role in maintaining glucose homeostasis by influencing the glucose transporters independently and through its receptors. The vast distribution of melatonin receptors in the body, including beta cells of pancreatic islets, asserts the role of this indole molecule in maintaining glucose homeostasis. Melatonin controls the production of GLUT4 and/or the phosphorylation process of the receptor for insulin and its intracellular substrates, activating the insulin-signalling pathway through its G-protein-coupled membrane receptors.
解决胰岛素抵抗或高胰岛素血症可能为阻止糖尿病性心肌病的发生提供可行的治疗方法，因为这些情况独立地导致疾病的发展，该疾病最初的特征是舒张异常。糖尿病性心肌病的发展似乎主要由胰岛素抵抗或胰岛素信号受损和/或高胰岛素血症驱动。氧化应激、肥大、纤维化、心脏舒张功能障碍以及最终的收缩性心力衰竭是这些病理生理改变的结果。褪黑素是一种普遍存在的吲哚胺，是一种广泛分布的化合物，主要由松果体分泌，几乎在每一种生物中都发挥着多种作用。褪黑素通过改善心肌细胞代谢、减少血管内皮细胞死亡、逆转微循环障碍、减少心肌纤维化、减少氧化和内质网应激、调节细胞自噬和凋亡以及增强线粒体功能，发挥主导作用。这篇综述强调了胰岛素抵抗与相关心肌病之间的关系。它探讨了神经激素褪黑素提供的潜在治疗策略，褪黑素是一种重要的抗氧化剂，通过独立影响葡萄糖转运体和通过其受体来影响葡萄糖稳态，在维持葡萄糖稳态方面发挥着主导作用。褪黑素受体在体内的广泛分布，包括胰岛β细胞，强调了这种吲哚分子在维持葡萄糖稳态中的作用。褪黑素控制 GLUT4 的产生和/或胰岛素及其细胞内底物的受体的磷酸化过程，通过其 G 蛋白偶联膜受体激活胰岛素信号通路。
