{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T12:22:01Z","timestamp":1768566121208,"version":"3.49.0"},"posted":{"date-parts":[[2023,3,29]]},"group-title":"Endocrinology (including Diabetes Mellitus and Metabolic Disease)","reference-count":44,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,3,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background\/Aims<\/jats:title>\n                  <jats:p>\n                    Prandial hyperinsulinemia after Roux-en Y gastric bypass surgery (GB), and to lesser degree after sleeve gastrectomy (SG), has been attributed to rapid glucose flux from the gut and increased insulinotropic gut hormones. However, \u03b2-cell sensitivity to\n                    <jats:italic>exogenous<\/jats:italic>\n                    incretin is markedly reduced after GB. This study examines the effect of GB versus SG on prandial glycemia and \u03b2-cell response to increasing concentrations of\n                    <jats:italic>endogenous<\/jats:italic>\n                    incretins.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Glucose kinetics, insulin secretion rate (ISR), and incretin responses to 50-gram oral glucose ingestion were compared between 10 non-diabetic subjects with GB versus 9 matched individuals with SG and 7 non-operated normal glucose tolerant controls (CN) on two days with and without administration of 200 mg sitagliptin.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Fasting glucose and hormonal levels were similar among 3 groups. Increasing plasma concentrations of endogenous incretins by 2-3-fold diminished post-OGTT glycemia and increased \u03b2-cell secretion in all 3 groups (p&lt;0.05), but insulin secretion per insulin sensitivity (i.e., disposition index) was increased only in GB (p&lt;0.05 for interaction). As a result, sitagliptin administration led to hypoglycemia in 3 of 10 GB. Yet, plot of the slope of ISR versus the increase in endogenous incretin concentration was smaller after GB compared to both SG and CN.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>\n                    Augmented glycemic-induced \u03b2-cell response caused by enhanced incretin activity is unique to GB and not shared with SG. However, the \u03b2-cell sensitivity to increasing concentrations of\n                    <jats:italic>endogenous<\/jats:italic>\n                    incretin is smaller after bariatric surgery, particularly after GB, compared to non-operated controls, indicating a long-term adaptation of gut-pancreas axis after these procedures.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>HIGHLIGHTS<\/jats:title>\n                  <jats:sec>\n                    <jats:title>What is known?<\/jats:title>\n                    <jats:p>\n                      Glycemic effects of gastric bypass (GB) and sleeve gastrectomy (SG) is attributed to rapid nutrient flux and enhanced insulinotropic effects of gut hormones but \u03b2-cell sensitivity to\n                      <jats:italic>exogenous<\/jats:italic>\n                      GLP-1 or GIP is diminished after GB.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>What the present findings add?<\/jats:title>\n                    <jats:p>\n                      Post-OGTT \u03b2-cell sensitivity to enhanced\n                      <jats:italic>endogenous<\/jats:italic>\n                      incretins by DPP4i is markedly reduced in bariatric subjects versus non-operated controls, and yet insulin secretory response (disposition index) is increased leading to hypoglycemia in GB and not SG.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance?<\/jats:title>\n                    <jats:p>Blunted sensitivity to GLP-1 may represent \u03b2-cell adaptation to massive elevation in GLP-1 secretion following bariatric surgery to protect against hypoglycemia.<\/jats:p>\n                    <jats:p>The differential effect of enhanced concentrations of incretins on post-OGTT insulin response (disposition index) among GB versus SG highlights a distinct adaptive process among the two procedures.<\/jats:p>\n                    <jats:p>Augmented insulinotropic effects of gut hormones on postprandial insulin secretory response after GB despite a reduced beta-cell sensitivity to plasma concentrations of GLP-1 makes a case for non-hormonal mechanisms of GLP-1 action after GB.<\/jats:p>\n                    <jats:p>Better understanding of long-term effects of bariatric surgery on gut-pancreas axis activity is critical in development of GLP-1-based strategies to address glucose abnormalities (both hyperglycemia and hypoglycemia) in these settings.<\/jats:p>\n                  <\/jats:sec>\n                <\/jats:sec>","DOI":"10.1101\/2023.03.28.23287755","type":"posted-content","created":{"date-parts":[[2023,3,29]],"date-time":"2023-03-29T17:00:23Z","timestamp":1680109223000},"source":"Crossref","is-referenced-by-count":2,"title":["Insulinotropic effect of endogenous incretins is greater after gastric bypass 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