{"doi":"10.1101/2023.10.22.23297377","title":"GLP-1 enhances beta-cell response to protein ingestion independent of glycemia and bariatric surgery amplifies it","abstract":"<jats:title>ABSTRACT</jats:title>\n                <jats:sec>\n                  <jats:title>Background</jats:title>\n                  <jats:p>The glycemic-independent actions of glucagon-like peptide 1 (GLP-1) in the prandial state in humans are largely unknown. Protein ingestion stimulates beta-cell secretion without changing plasma glucose concentration. We examined the contribution of endogenous GLP-1 to glucose metabolism and beta-cell response to protein ingestion under basal glucose concentrations, and whether these responses are affected by rerouted gut after gastric bypass (GB) or sleeve gastrectomy (SG).</jats:p>\n                </jats:sec>\n                <jats:sec>\n                  <jats:title>Methods</jats:title>\n                  <jats:p>Insulin secretion rate (ISR) and glucose fluxes during 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.</jats:p>\n                </jats:sec>\n                <jats:sec>\n                  <jats:title>Results</jats:title>\n                  <jats:p>\n                    Blocking GLP-1R increased plasma glucose concentration before and after protein ingestion and decreased beta-cell sensitivity to glucose in the first 30 minutes of protein ingestion (p&lt;0.05) in all 3 groups. However, reduction in the premeal ISR by Ex-9 infusion only was observed in CN (p&lt;0.05 for interaction), whereas diminished prandial ISR\n                    <jats:sub>3h</jats:sub>\n                    by GLP-1R blockade was observed in GB and SG and not in controls (p&lt;0.05 for interaction). Also, GLP-1R blockade enhanced post-protein insulin action in GB and SG, but not in CN. Endogenous glucose production (\n                    <jats:italic>EGP</jats:italic>\n                    ) during the first hour after protein ingestion was increased in all 3 groups but\n                    <jats:italic>EGP</jats:italic>\n                    <jats:sub>3h</jats:sub>\n                    was accentuated by Ex-9 infusion only in GB (p&lt;0.05 for interaction).\n                  </jats:p>\n                </jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion</jats:title>\n                  <jats:p>These findings are consistent with both a glucose-independent pancreatic and extra-pancreatic role for GLP-1 during protein ingestion in humans that are exaggerated by bariatric surgery.</jats:p>\n                </jats:sec>\n                <jats:sec>\n                  <jats:title>Trial registration</jats:title>\n                  <jats:p>\n                    This study was registered at Clinical Trials.Gov:\n                    <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT02823665\">NCT02823665</jats:ext-link>\n                  </jats:p>\n                </jats:sec>","journal":null,"year":null,"id":620234,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":476977,"name":"Amalia Gastaldelli","orcid":"0000-0003-2594-1651","position":1,"is_corresponding":false},{"id":490636,"name":"Henri Honka","orcid":"0000-0003-1389-6355","position":2,"is_corresponding":false},{"id":1601066,"name":"Samantha Pezzica","orcid":null,"position":3,"is_corresponding":false},{"id":1036737,"name":"Fabrizia Carli","orcid":"0000-0003-2540-1110","position":4,"is_corresponding":false},{"id":1601069,"name":"Richard Peterson","orcid":null,"position":5,"is_corresponding":false},{"id":1601071,"name":"Ralph DeFronzo","orcid":null,"position":6,"is_corresponding":false},{"id":801085,"name":"Marzieh Salehi","orcid":"0000-0003-4764-739X","position":7,"is_corresponding":false},{"id":875365,"name":"Maria Rayas","orcid":"0000-0001-8658-7831","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"GLP-1 enhances beta-cell response to protein ingestion independent of glycemia and bariatric surgery amplifies it","abstract":"<jats:title>ABSTRACT</jats:title>\n                <jats:sec>\n                  <jats:title>Background</jats:title>\n                  <jats:p>The glycemic-independent actions of glucagon-like peptide 1 (GLP-1) in the prandial state in humans are largely unknown. Protein ingestion stimulates beta-cell secretion without changing plasma glucose concentration. We examined the contribution of endogenous GLP-1 to glucose metabolism and beta-cell response to protein ingestion under basal glucose concentrations, and whether these responses are affected by rerouted gut after gastric bypass (GB) or sleeve gastrectomy (SG).</jats:p>\n                </jats:sec>\n                <jats:sec>\n                  <jats:title>Methods</jats:title>\n                  <jats:p>Insulin secretion rate (ISR) and glucose fluxes during 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.</jats:p>\n                </jats:sec>\n                <jats:sec>\n                  <jats:title>Results</jats:title>\n                  <jats:p>\n                    Blocking GLP-1R increased plasma glucose concentration before and after protein ingestion and decreased beta-cell sensitivity to glucose in the first 30 minutes of protein ingestion (p&lt;0.05) in all 3 groups. However, reduction in the premeal ISR by Ex-9 infusion only was observed in CN (p&lt;0.05 for interaction), whereas diminished prandial ISR\n                    <jats:sub>3h</jats:sub>\n                    by GLP-1R blockade was observed in GB and SG and not in controls (p&lt;0.05 for interaction). Also, GLP-1R blockade enhanced post-protein insulin action in GB and SG, but not in CN. Endogenous glucose production (\n                    <jats:italic>EGP</jats:italic>\n                    ) during the first hour after protein ingestion was increased in all 3 groups but\n                    <jats:italic>EGP</jats:italic>\n                    <jats:sub>3h</jats:sub>\n                    was accentuated by Ex-9 infusion only in GB (p&lt;0.05 for interaction).\n                  </jats:p>\n                </jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion</jats:title>\n                  <jats:p>These findings are consistent with both a glucose-independent pancreatic and extra-pancreatic role for GLP-1 during protein ingestion in humans that are exaggerated by bariatric surgery.</jats:p>\n                </jats:sec>\n                <jats:sec>\n                  <jats:title>Trial registration</jats:title>\n                  <jats:p>\n                    This study was registered at Clinical Trials.Gov:\n                    <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT02823665\">NCT02823665</jats:ext-link>\n                  </jats:p>\n                </jats:sec>","is_dataset_classified":null,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"37961500","pmcid":null,"openalex_id":"https://openalex.org/W4387868998","authors":[],"funders":[],"total_grants":0,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[{"year":2025,"count":1}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://www.medrxiv.org/content/medrxiv/early/2023/10/23/2023.10.22.23297377.full.pdf","host_type":"repository"},{"url":"https://www.medrxiv.org/content/medrxiv/early/2023/10/23/2023.10.22.23297377.full.pdf","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.1101/2023.10.22.23297377","host_type":"publisher"},{"url":"https://doi.org/10.1101/2023.10.22.23297377","host_type":"repository"},{"url":"https://pubmed.ncbi.nlm.nih.gov/37961500","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/10635165","host_type":"repository"}],"fields_of_study":["Bariatric Surgery and Outcomes","Diabetes Treatment and Management","Hyperglycemia and glycemic control in critically ill and hospitalized patients"],"mesh_terms":[],"keywords":["Ingestion","BETA (programming language)","Beta cell","Medicine","Surgery","Internal medicine","Diabetes mellitus","Endocrinology","Computer science"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-03T10:27:14.970505Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}