GLP-1 enhances beta-cell response to protein ingestion and bariatric surgery amplifies it.
Autor: | Rayas M, Gastaldelli A, Honka H, Pezzica S, Carli F, Peterson R, DeFronzo R, Salehi MS |
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Jazyk: | angličtina |
Zdroj: | MedRxiv : the preprint server for health sciences [medRxiv] 2024 Jan 11. Date of Electronic Publication: 2024 Jan 11. |
DOI: | 10.1101/2023.10.22.23297377 |
Abstrakt: | Objective: Protein ingestion stimulates β-cell secretion and alters glucose flux. Enhanced action of glucagon-like peptide 1 (GLP-1) and increased plasma glucose excursion contribute to prandial hyperinsulinemia after gastric bypass surgery (GB) and sleeve gastrectomy (SG). We examined the contribution of endogenous GLP-1 to glucose kinetics and β-cell response to protein ingestion under basal glucose concentrations in humans, and whether these responses are affected by rerouted gut after GB or SG. Design: Glucose fluxes, insulin secretion rate (ISR), and incretin responses to a 50-gram oral protein load were compared between 10 non-diabetic individuals with GB, 9 matched subjects with SG and 7 non-operated controls (CN) with and without intravenous infusion of exendin-(9- 39) [Ex-9), a specific GLP-1 receptor (GLP-1R) antagonist. Results: Blocking GLP-1R increased the plasma glucose concentration before and after protein ingestion in all 3 groups (p<0.05) and decreased β-cell sensitivity to glucose in the first 30 minutes of protein ingestion (p<0.05). Reduction in the prandial ISR3h by Ex-9 infusion, however, only was observed in GB and SG (p<0.05 for interaction) and not in controls. Also, GLP-1R blockade increased post-protein insulin action in GB and SG, but not CN (p=0.09 for interaction). Endogenous glucose production (EGP) during the first 60 minutes after protein ingestion was increased in all 3 groups but EGP3h only was accentuated in GB by Ex-9 infusion (p<0.05 for interaction). Conclusion: These findings are consistent with both a pancreatic and extrapancreatic role for GLP-1 during protein ingestion in humans, and GLP-1 actions are exaggerated by bariatric surgery. |
Databáze: | MEDLINE |
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