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 病理生理学的分子机制是改进当前疗法的关键。蛋白质稳态的丧失导致细胞中受损蛋白质的积累，从而导致组织功能障碍。受损蛋白质的消除通过泛素-蛋白酶体系统 (UPS) 和自噬发生。在这篇综述中，我们描述了 UPS 和自噬之间的相互调节以及这两种蛋白水解系统在代谢失调、胰岛素抵抗和 T2DM 中的作用。我们建议 UPS 或自噬的改变有助于触发胰岛素抵抗和 T2DM 的发展。此外，这两种途径成为改善胰岛素抵抗的有希望的治疗靶点。