小柯机器人

丹麦哥本哈根大学Erik A. Richter和瑞士联邦理工学院Katrien De Bock共同合作，近期取得重要工作进展。他们研究发现，GDF15通过β-肾上腺素能受体介导的机制增加胰岛素在肝脏和脂肪组织中的作用。相关研究成果2023年7月19日在西安发表于《细胞—代谢》杂志上。

据介绍，生长分化因子15（GDF15）在肥胖啮齿动物中诱导体重减轻并增加胰岛素作用。GDF15是否以及如何在不减轻体重的情况下改善胰岛素作用尚不清楚。

用GDF15治疗肥胖大鼠，并在5小时后显示出胰岛素耐受性增加。在第1天、第3天和第5天用GDF15治疗瘦和肥胖的雌性和雄性小鼠，没有减轻体重，并且在第6天的正常血糖高胰岛素钳夹期间，由于WAT和BAT中内源性葡萄糖产生的抑制增强和葡萄糖摄取的增加，显示出胰岛素敏感性增加。GDF15在钳夹过程中也降低了胰高血糖素水平，与GFRAL受体无关。GDF15的胰岛素增敏作用在GFRAL 敲除小鼠中完全消除，也通过β-肾上腺素能拮抗剂普萘洛尔和β1，β2-肾上腺素能受体敲除小鼠的治疗完全消除。

总之，研究人员发现，GFRAL受体的GDF15激活增加了β-肾上腺素能信号传导，进而改善了胰岛素在肝脏、白色和棕色脂肪组织中的作用。

附：英文原文

Title: GDF15 increases insulin action in the liver and adipose tissue via a β-adrenergic receptor-mediated mechanism

Author: Kim A. Sjberg, Casper M. Sigvardsen, Abdiel Alvarado-Diaz, Nicoline Resen Andersen, Mark Larance, Randy J. Seeley, Peter Schjerling, Jakob G. Knudsen, Georgios Katzilieris-Petras, Christoffer Clemmensen, Sebastian Beck Jrgensen, Katrien De Bock, Erik A. Richter

Issue&Volume: 2023-07-19

Abstract: Growth differentiation factor 15 (GDF15) induces weight loss and increases insulinaction in obese rodents. Whether and how GDF15 improves insulin action without weightloss is unknown. Obese rats were treated with GDF15 and displayed increased insulintolerance 5 h later. Lean and obese female and male mice were treated with GDF15 ondays 1, 3, and 5 without weight loss and displayed increased insulin sensitivity duringa euglycemic hyperinsulinemic clamp on day 6 due to enhanced suppression of endogenousglucose production and increased glucose uptake in WAT and BAT. GDF15 also reducedglucagon levels during clamp independently of the GFRAL receptor. The insulin-sensitizingeffect of GDF15 was completely abrogated in GFRAL KO mice and also by treatment withthe β-adrenergic antagonist propranolol and in β1,β2-adrenergic receptor KO mice.GDF15 activation of the GFRAL receptor increases β-adrenergic signaling, in turn,improving insulin action in the liver and white and brown adipose tissue.

DOI: 10.1016/j.cmet.2023.06.016

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00226-7

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
官方网址：https://www.cell.com/cell-metabolism/home
投稿链接：https://www.editorialmanager.com/cell-metabolism/default.aspx