Rayas Maria, Pezzica Samantha, Honka Henri, Carli Fabrizia, Peterson Richard, DeFronzo Ralph, Gastaldelli Amalia, Salehi Marzieh
Department of Pediatrics, University of Texas Health at San Antonio, San Antonio, Texas, USA.
Cardiometabolic Risk Unit, CNR Institute of Clinical Physiology, Pisa, Italy.
Obesity (Silver Spring). 2025 Jan;33(1):104-115. doi: 10.1002/oby.24182. Epub 2024 Dec 5.
The glycemic-independent actions of glucagon-like peptide-1 (GLP-1) in the prandial state in humans are unknown. We examined the contribution of GLP-1 to β-cell secretory response (primary endpoint) and glucose metabolism during protein ingestion under basal glycemia, as well as whether these responses are affected by rerouted gut after gastric bypass (GB) or sleeve gastrectomy (SG).
Insulin secretion rate (ISR) and glucose fluxes during a 50-g oral protein load were compared among 10 nondiabetic individuals with GB, 9 with SG, and 7 non-operated controls (CN), with and without intravenous infusion of exendin(9-39) (Ex-9), a GLP-1 receptor (GLP-1R) antagonist.
Blocking GLP-1R increased glucose before and after protein ingestion and decreased β-cell sensitivity to glucose in the first 30 min of protein ingestion in all three groups (p < 0.05). Reduction in the premeal ISR by Ex-9 infusion was only observed in CN, whereas diminished prandial ISR by GLP-1R blockade was only observed in GB and SG (p < 0.05 for interaction). GLP-1R blockade enhanced post-protein insulin action in GB and SG, but not in CN, and exaggerated endogenous glucose production only GB (p < 0.05 for interaction).
These findings are consistent with both pancreatic and extra-pancreatic roles for GLP-1 during protein ingestion in humans that are exaggerated by bariatric surgery.
胰高血糖素样肽-1（GLP-1）在人类进食状态下不依赖血糖的作用尚不清楚。我们研究了在基础血糖水平下蛋白质摄入期间GLP-1对β细胞分泌反应（主要终点）和葡萄糖代谢的贡献，以及这些反应是否受胃旁路手术（GB）或袖状胃切除术（SG）后肠道改道的影响。
比较了10例接受GB的非糖尿病个体、9例接受SG的非糖尿病个体和7例未手术的对照者（CN）在口服50克蛋白质负荷期间的胰岛素分泌率（ISR）和葡萄糖通量，分别在静脉输注艾塞那肽（9-39）（Ex-9）（一种GLP-1受体（GLP-1R）拮抗剂）前后进行比较。
阻断GLP-1R可增加三组人群在蛋白质摄入前后的血糖水平，并降低蛋白质摄入后最初30分钟内β细胞对葡萄糖的敏感性（p<0.05）。仅在CN组中观察到输注Ex-9后空腹ISR降低，而仅在GB组和SG组中观察到GLP-1R阻断导致餐后ISR降低（交互作用p<0.05）。GLP-1R阻断增强了GB组和SG组蛋白质摄入后的胰岛素作用，但在CN组中未增强，并且仅在GB组中夸大了内源性葡萄糖生成（交互作用p<0.05）。
这些发现与GLP-1在人类蛋白质摄入期间在胰腺和胰腺外的作用一致，而减肥手术会夸大这些作用。
