Department of Pharmacology, Toxicology and Therapeutic Chemistry, Institute of Biomedicine of the University of Barcelona (IBUB), Faculty of Pharmacy and Food Sciences, University of Barcelona, Avinguda Joan XXIII 27-31, 08028 Barcelona, Spain.
Pediatric Research Institute-Hospital Sant Joan de Déu, 08950 Esplugues de Llobregat, Spain.
Int J Mol Sci. 2021 Aug 9;22(16):8555. doi: 10.3390/ijms22168555.
The current treatment options for type 2 diabetes mellitus do not adequately control the disease in many patients. Consequently, there is a need for new drugs to prevent and treat type 2 diabetes mellitus. Among the new potential pharmacological strategies, activators of peroxisome proliferator-activated receptor (PPAR)β/δ show promise. Remarkably, most of the antidiabetic effects of PPARβ/δ agonists involve AMP-activated protein kinase (AMPK) activation. This review summarizes the recent mechanistic insights into the antidiabetic effects of the PPARβ/δ-AMPK pathway, including the upregulation of glucose uptake, muscle remodeling, enhanced fatty acid oxidation, and autophagy, as well as the inhibition of endoplasmic reticulum stress and inflammation. A better understanding of the mechanisms underlying the effects resulting from the PPARβ/δ-AMPK pathway may provide the basis for the development of new therapies in the prevention and treatment of insulin resistance and type 2 diabetes mellitus.
目前，2 型糖尿病的治疗选择并不能使许多患者的病情得到充分控制。因此，需要新的药物来预防和治疗 2 型糖尿病。在新的潜在药理学策略中，过氧化物酶体增殖物激活受体（PPAR）β/δ 的激活剂显示出前景。值得注意的是，PPARβ/δ 激动剂的大多数抗糖尿病作用都涉及 AMP 激活的蛋白激酶（AMPK）的激活。本文综述了最近关于 PPARβ/δ-AMPK 通路的抗糖尿病作用的机制见解，包括葡萄糖摄取、肌肉重塑、增强脂肪酸氧化和自噬的上调，以及内质网应激和炎症的抑制。更好地了解 PPARβ/δ-AMPK 通路作用的机制可能为预防和治疗胰岛素抵抗和 2 型糖尿病提供新的治疗方法的基础。
