敲开 GDF15 的大门治疗 2 型糖尿病。

Knocking on GDF15's door for the treatment of type 2 diabetes mellitus.

机构信息

Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain; Institute of Biomedicine of the University of Barcelona (IBUB), Barcelona, Spain; Pediatric Research Institute-Hospital Sant Joan de Déu, Barcelona, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas, Instituto de Salud Carlos III, Avinguda Joan XXII 27-31, E-08028 Barcelona, Spain.

Center for Integrative Genomics, University of Lausanne, CH-1015 Lausanne, Switzerland; Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Singapore 308232; ToxAlim (Research Center in Food Toxicology), INRAE, UMR1331, 31300 Toulouse Cedex, France.

出版信息

Trends Endocrinol Metab. 2022 Nov;33(11):741-754. doi: 10.1016/j.tem.2022.08.004. Epub 2022 Sep 20.

DOI:10.1016/j.tem.2022.08.004

PMID:36151002

Abstract

Although a large number of drugs are available for the treatment of type 2 diabetes mellitus (T2DM), many patients do not achieve adequate disease control despite adhering to medication. Recent findings indicate that the pharmacological modulation of the stress-induced cytokine growth differentiation factor 15 (GDF15) shows promise for the treatment of T2DM. GDF15 suppresses appetite and reduces inflammation, increases thermogenesis and lipid catabolism, sustains AMP-activated protein kinase (AMPK) activity, and ameliorates insulin resistance and hepatic steatosis. In addition, circulating GDF15 levels are elevated in response to several antidiabetic drugs, including metformin, with GDF15 mediating some of their effects. Here, we review the mechanistic insights into the beneficial effects of recently explored therapeutic approaches that target GDF15 for the treatment of T2DM.

摘要

尽管有大量药物可用于治疗 2 型糖尿病（T2DM），但许多患者即使坚持用药也无法达到充分的疾病控制。最近的研究结果表明，应激诱导的细胞因子生长分化因子 15（GDF15）的药理学调节可能对 T2DM 的治疗有帮助。GDF15 可抑制食欲和减轻炎症，增加产热和脂肪分解，维持 AMP 激活的蛋白激酶（AMPK）的活性，并改善胰岛素抵抗和肝脂肪变性。此外，循环 GDF15 水平在响应几种抗糖尿病药物（包括二甲双胍）时会升高，其中 GDF15 介导了它们的一些作用。在这里，我们回顾了最近探索的针对 GDF15 治疗 T2DM 的治疗方法的有益作用的机制见解。