Introduction and Objective: Glucagon influences glucose tolerance by increasing nutrient-induced insulin secretion. After gastric bypass (GB), prandial glucagon levels rise, independent of the nutrient composition, and remain elevated in the latter phase of the meal, when glycemia dips below fasting level. Here, we investigated the effect of hyperglucagonemia (100-150 pg/ml), created by ‘exogenous glucagon infusion’, on prandial insulin secretion, clearance and glucose fluxes.Methods: Nine non-diabetic subjects with prior history of GB and seven healthy non-operated controls (CN), matched for age, BMI, FFM, A1C, were studied twice, with and without intravenous glucagon infusion (2ng/kg/min) during a 3-hr liquid mixed meal test (50-gram whey protein + 50-gram glucose).Results: Fasting levels of glucose and islet hormones were similar between the 2 studies and among groups. As expected, prandial glucose and insulin secretion shifted to the left and upward in GB compared to CN. Prandial glucagon levels in GB were 1.5 times as high as in CN. Glucagon infusion further increased plasma concentrations by 1.5-fold in each group but had no effect on prandial β-cell secretory response or insulin clearance. Endogenous glucose production, insulin action (metabolic clearance of glucose/ insulin) and glucose tolerance were unaffected by glucagon infusion, but systemic appearance of ingested glucose (RaOral) was significantly reduced (p<0.05) by glucagon infusion in both GB and CN.Conclusion: Our findings indicate that increasing systemic glucagon concentrations within physiological levels has no effect on the overall prandial glucose or insulin secretory response in subjects with normal glucose tolerance with or without bariatric surgery. Whether the excess post-meal ‘endogenous glucagon’ response after GB contribute to glucose metabolism needs further studies.
A. Gastaldelli: Advisory Panel; Boehringer-Ingelheim. Consultant; Boehringer-Ingelheim, Novo Nordisk, Merck Sharp & Dohme Corp, Regeneron Pharmaceuticals. Other Relationship; Pfizer Inc, Madrigal Pharmaceuticals, Inc, Echosens, Eli Lilly and Company. Speaker’s Bureau; Merck Sharp & Dohme Corp, Eli Lilly and Company, Novo Nordisk. A. Alamari: None. S. Pezzica: None. M. Salehi: Advisory Panel; Vognex, Amylyx.
National Institutes of Health DK105379 (MS)
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