泛素-蛋白酶体系统与自噬：为代谢健康进行自我消化。
The ubiquitin-proteasome system and autophagy: self-digestion for metabolic health.
作者信息
Sun-Wang Jia Liang, Yarritu-Gallego Alex, Ivanova Saška, Zorzano Antonio
机构信息
Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain; Departament de Bioquímica i Biomedicina Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas, Barcelona, Spain.
Department of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin Berlin, Berlin, Germany; Experimental and Clinical Research Center, a Cooperation of Charité-Universitätsmedizin Berlin and Max Delbruck Center for Molecular Medicine, Berlin, Germany.
出版信息
Trends Endocrinol Metab. 2021 Aug;32(8):594-608. doi: 10.1016/j.tem.2021.04.015. Epub 2021 May 22.
Type 2 diabetes mellitus (T2DM) is a global health challenge. Therefore, understanding the molecular mechanisms underlying the pathophysiology of T2DM is key to improving current therapies. Loss of protein homeostasis leads to the accumulation of damaged proteins in cells, which results in tissue dysfunction. The elimination of damaged proteins occurs through the ubiquitin-proteasome system (UPS) and autophagy. In this review, we describe the mutual regulation between the UPS and autophagy and the involvement of these two proteolytic systems in metabolic dysregulation, insulin resistance, and T2DM. We propose that alterations in the UPS or autophagy contribute to triggering insulin resistance and the development of T2DM. In addition, these two pathways emerge as promising therapeutic targets for improving insulin resistance.
2型糖尿病（T2DM）是一项全球性的健康挑战。因此，了解T2DM病理生理学背后的分子机制是改善当前治疗方法的关键。蛋白质稳态的丧失会导致受损蛋白质在细胞内积累，进而导致组织功能障碍。受损蛋白质的清除通过泛素-蛋白酶体系统（UPS）和自噬进行。在本综述中，我们描述了UPS和自噬之间的相互调节以及这两个蛋白水解系统在代谢失调、胰岛素抵抗和T2DM中的作用。我们提出，UPS或自噬的改变有助于引发胰岛素抵抗和T2DM的发展。此外，这两条途径有望成为改善胰岛素抵抗的治疗靶点。
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