Galizzi Giacoma, Di Carlo Marta
Istituto per la Ricerca e l'Innovazione Biomedica (IRIB) CNR, Via Ugo la Malfa, 153, 90146 Palermo, Italy.
Biology (Basel). 2022 Jun 20;11(6):943. doi: 10.3390/biology11060943.
Insulin was discovered and isolated from the beta cells of pancreatic islets of dogs and is associated with the regulation of peripheral glucose homeostasis. Insulin produced in the brain is related to synaptic plasticity and memory. Defective insulin signaling plays a role in brain dysfunction, such as neurodegenerative disease. Growing evidence suggests a link between metabolic disorders, such as diabetes and obesity, and neurodegenerative diseases, especially Alzheimer's disease (AD). This association is due to a common state of insulin resistance (IR) and mitochondrial dysfunction. This review takes a journey into the past to summarize what was known about the physiological and pathological role of insulin in peripheral tissues and the brain. Then, it will land in the present to analyze the insulin role on mitochondrial health and the effects on insulin resistance and neurodegenerative diseases that are IR-dependent. Specifically, we will focus our attention on the quality control of mitochondria (MQC), such as mitochondrial dynamics, mitochondrial biogenesis, and selective autophagy (mitophagy), in healthy and altered cases. Finally, this review will be projected toward the future by examining the most promising treatments that target the mitochondria to cure neurodegenerative diseases associated with metabolic disorders.
胰岛素是从狗的胰岛β细胞中发现并分离出来的，与外周葡萄糖稳态的调节有关。大脑中产生的胰岛素与突触可塑性和记忆有关。胰岛素信号缺陷在脑功能障碍中起作用，如神经退行性疾病。越来越多的证据表明，代谢紊乱，如糖尿病和肥胖，与神经退行性疾病，尤其是阿尔茨海默病（AD）之间存在联系。这种关联是由于共同的胰岛素抵抗（IR）状态和线粒体功能障碍。本综述回顾过去，总结胰岛素在周围组织和大脑中的生理和病理作用。然后，将着眼当下，分析胰岛素对线粒体健康的作用以及对依赖IR的胰岛素抵抗和神经退行性疾病的影响。具体而言，我们将关注健康和病变情况下线粒体的质量控制（MQC），如线粒体动力学、线粒体生物发生和选择性自噬（线粒体自噬）。最后，本综述将展望未来，研究最有前景的针对线粒体的治疗方法，以治愈与代谢紊乱相关的神经退行性疾病。
