University of Barcelona, Department of Pharmacology and Therapeutic Chemistry, Barcelona, Spain.
Expert Opin Ther Targets. 2012 Feb;16(2):209-23. doi: 10.1517/14728222.2012.658370. Epub 2012 Jan 27.
The nuclear receptors Peroxisome Proliferator-Activated Receptors (PPAR)α and PPARγ are therapeutic targets for hypertriglyceridemia and insulin resistance, respectively. Evidence is now emerging that the PPARβ/δ isotype is a potential pharmacological target for the treatment of insulin resistance and type 2 diabetes mellitus.
In this review, the capacity of PPARβ/δ to prevent the development of insulin resistance and type 2 diabetes mellitus is discussed. Special emphasis is placed on preclinical studies and the molecular mechanisms responsible for its actions in the main cell types involved in these pathologies: adipocytes, β-cells, skeletal muscle cells and hepatocytes.
While several concerns remain for the development of PPARβ/δ agonists, these drugs have demonstrated their efficacy in the treatment of insulin resistance and type 2 diabetes mellitus in preclinical studies, as well as in a few short clinical studies in humans. Although this data is promising, additional studies must be performed to confirm the efficacy and safety of these drugs in the treatment of type 2 diabetes mellitus.
过氧化物酶体增殖物激活受体（PPAR）α 和 PPARγ 是分别治疗高甘油三酯血症和胰岛素抵抗的治疗靶点。现在有证据表明，PPARβ/δ 同工型可能是治疗胰岛素抵抗和 2 型糖尿病的潜在药物靶点。
本文讨论了 PPARβ/δ 预防胰岛素抵抗和 2 型糖尿病发生的能力。特别强调了其在涉及这些疾病的主要细胞类型（脂肪细胞、β 细胞、骨骼肌细胞和肝细胞）中的作用的临床前研究和分子机制。
虽然开发 PPARβ/δ 激动剂仍存在一些问题，但这些药物在临床前研究以及少数人类短期临床研究中已证明其在治疗胰岛素抵抗和 2 型糖尿病方面的疗效。尽管这些数据很有希望，但仍需要进行更多的研究来确认这些药物在治疗 2 型糖尿病方面的疗效和安全性。
