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. 2025 Jan;33(1):104-115.
doi: 10.1002/oby.24182. Epub 2024 Dec 5.

GLP-1 enhances β-cell response to protein ingestion and bariatric surgery amplifies it

Maria Rayas  1 , Samantha Pezzica  2 , Henri Honka  3 , Fabrizia Carli  2 , Richard Peterson  4 , Ralph DeFronzo  3 , Amalia Gastaldelli  2   3 , Marzieh Salehi  3   5
Affiliations

GLP-1 enhances β-cell response to protein ingestion and bariatric surgery amplifies it

Maria Rayas et al. Obesity (Silver Spring). 2025 Jan.

Abstract

Objective: 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).

Methods: 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.

Results: 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 ISR3h 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).

Conclusions: 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.

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