解析 PPARβ/δ 对胰岛素抵抗和心血管疾病的影响。
Unraveling the Effects of PPARβ/δ on Insulin Resistance and Cardiovascular Disease.
机构信息
Department of Pharmacology and Therapeutic Chemistry, Faculty of Pharmacy, University of Barcelona, Institute of Biomedicine of the University of Barcelona (IBUB), Pediatric Research Institute, Hospital Sant Joan de Déu, Barcelona, Spain; Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Diseases (CIBERDEM)-Instituto de Salud Carlos III, Diagonal 643, 08028 Barcelona, Spain.
出版信息
Trends Endocrinol Metab. 2016 May;27(5):319-334. doi: 10.1016/j.tem.2016.02.008. Epub 2016 Mar 20.
Insulin resistance precedes dyslipidemia and type 2 diabetes mellitus (T2DM) development. Preclinical evidence suggests that peroxisome proliferator-activated receptor (PPAR) β/δ activators may prevent and treat obesity-induced insulin resistance and T2DM, while clinical trials highlight their potential utility in dyslipidemia. This review summarizes recent mechanistic insights into the antidiabetic effects of PPARβ/δ activators, including their anti-inflammatory actions, their ability to inhibit endoplasmic reticulum (ER) stress and hepatic lipogenesis, and to improve atherogenesis and insulin sensitivity, as well as their capacity to activate pathways that are also stimulated by exercise. Findings from clinical trials are also examined. Dissecting the effects of PPARβ/δ ligands on insulin sensitivity and atherogenesis may provide a basis for the development of therapies for the prevention and treatment of T2DM and cardiovascular disease (CVD).
胰岛素抵抗先于血脂异常和 2 型糖尿病（T2DM）的发生。临床前证据表明，过氧化物酶体增殖物激活受体（PPAR）β/δ 激动剂可能预防和治疗肥胖引起的胰岛素抵抗和 T2DM，而临床试验则强调了它们在血脂异常方面的潜在用途。本文综述了 PPARβ/δ 激动剂在糖尿病方面的最新作用机制，包括其抗炎作用、抑制内质网（ER）应激和肝脂肪生成、改善动脉粥样硬化和胰岛素敏感性的能力，以及激活运动也能刺激的途径的能力。还检查了临床试验的结果。剖析 PPARβ/δ 配体对胰岛素敏感性和动脉粥样硬化的影响可能为预防和治疗 T2DM 和心血管疾病（CVD）的治疗提供基础。
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