Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA.
First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece.
Diabetes Metab Res Rev. 2020 Jul;36(5):e3297. doi: 10.1002/dmrr.3297. Epub 2020 Mar 1.
Follistatin binds and inactivates activins, which are potent inhibitors of muscle growth and metabolism and are currently being developed for the treatment of obesity and type 2 diabetes (T2D). We have recently reported that follistatin is regulated by glucose (and not lipids) and can prospectively predict the metabolic improvements observed after bariatric surgery. We utilized novel assays herein to investigate whether activins are regulated by glucose or lipids, whether their circulating levels change after bariatric surgery and whether these changes are predictors of metabolic outcomes up to 12 months later.
Activin A, B, AB and their ratios to follistatin were measured in (a) healthy humans (n = 32) undergoing oral or intravenous lipid or glucose intake over 6 h, (b) morbidly obese individuals with or without type 2 diabetes undergoing three different types of bariatric surgery (gastric banding, Roux-en-Y bypass or sleeve gastrectomy) in two clinical studies (n = 14 for the first and n = 27 for the second study).
Glucose intake downregulates circulating activin A, B and AB, indicating the presence of a feedback loop. Activin A decreases (30%), activin AB increases (25%) and activin B does not change after bariatric surgery. The changes in activin AB and its ratio to follistatin 3 months after bariatric surgery can predict the BMI reduction and the improvement in insulin and HOMA-IR observed 6 months postoperatively.
Activins are implicated in glucose regulation in humans as part of a feedback loop with glucose or insulin and predict metabolic outcomes prospectively after bariatric surgery.
卵泡抑素能与激活素结合并使其失活，激活素是肌肉生长和代谢的强效抑制剂，目前正在开发用于治疗肥胖症和 2 型糖尿病（T2D）。我们最近报道，卵泡抑素受葡萄糖（而非脂质）调控，并可前瞻性预测减重手术后观察到的代谢改善。我们利用新的检测方法来研究激活素是否受葡萄糖或脂质调控，减重手术后其循环水平是否发生变化，以及这些变化是否可以预测术后 12 个月的代谢结果。
在（a）健康人群（n=32）接受 6 小时口服或静脉内脂质或葡萄糖摄入后，测量激活素 A、B、AB 及其与卵泡抑素的比值；（b）患有 2 型糖尿病或无 2 型糖尿病的病态肥胖患者接受三种不同类型的减重手术（胃束带、Roux-en-Y 旁路或袖状胃切除术），在两项临床研究中（第一项研究 n=14，第二项研究 n=27）。
葡萄糖摄入可下调循环激活素 A、B 和 AB，表明存在反馈回路。减重手术后激活素 A 降低（约 30%），激活素 AB 增加（约 25%），激活素 B 不变。减重手术后 3 个月激活素 AB 的变化及其与卵泡抑素的比值可预测术后 6 个月 BMI 降低和胰岛素及 HOMA-IR 的改善。
激活素参与人类葡萄糖调节，作为与葡萄糖或胰岛素的反馈回路的一部分，可前瞻性预测减重手术后的代谢结果。
