Differential incretin effects of GIP and GLP‐1 on gastric emptying, appetite, and insulin‐glucose homeostasis

Background  Glucose‐dependent insulinotropic polypeptide (GIP) and glucagon‐like peptide‐1 (GLP‐1) are major incretins with important effects on glucoregulatory functions. The aim of this study was to investigate effects of GIP and GLP‐1 on gastric emptying and appetite after a mixed meal, and effec...

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Published inNeurogastroenterology and motility Vol. 22; no. 11; pp. 1191 - e315
Main Authors Edholm, T., Degerblad, M., Grybäck, P., Hilsted, L., Holst, J. J., Jacobsson, H., Efendic, S., Schmidt, P. T., Hellström, P. M.
Format Journal Article
LanguageEnglish
Published Oxford, UK Blackwell Publishing Ltd 01.11.2010
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Summary:Background  Glucose‐dependent insulinotropic polypeptide (GIP) and glucagon‐like peptide‐1 (GLP‐1) are major incretins with important effects on glucoregulatory functions. The aim of this study was to investigate effects of GIP and GLP‐1 on gastric emptying and appetite after a mixed meal, and effects on insulin secretion and glucose disposal in humans. Methods  Randomized crossover single‐blind study in 17 healthy volunteers receiving GIP (2 or 5 pmol kg−1 min−1, n = 8), GLP‐1 (0.75 pmol kg−1 min−1, n = 9) or NaCl for 180 min with a radionuclide‐labeled omelette and fruit punch (370 kcal). Outcome measures were gastric emptying rate, insulinogenic index, hunger, satiety, desire to eat, and prospective food consumption. Blood was analyzed for GIP, GLP‐1, glucagon, C‐peptide, peptide YY (PYY) and ghrelin. Key Results  Glucose‐dependent insulinotropic polypeptide 2 and 5 pmol kg−1 min−1 decreased gastric half‐emptying time from 128.5 ± 34.0 min in controls to 93.3 ± 6.3 and 85.2 ± 11.0 min (P < 0.05). Glucose‐dependent insulinotropic polypeptide 5 pmol kg−1 min−1 decreased postprandial glucose (P < 0.001) and insulin (P < 0.05) with increased insulinogenic index. Glucose‐dependent insulinotropic polypeptide had no effects on hunger, desire to eat, satiety or prospective consumption. Glucagon‐like peptide‐1 0.75 pmol kg−1 min−1 increased half‐emptying time from 76.6 ± 7.6 min to 329.4 ± 71.6 (P < 0.01). Glucagon‐like peptide‐1 decreased plasma glucose and insulin (both P < 0.05–0.001), and increased insulinogenic index markedly. Hunger, desire to eat and prospective consumption were decreased (P < 0.05), and satiety borderline increased (P < 0.06). Conclusion & Inferences  The incretin effect of GIP and GLP‐1 differs as GLP‐1 exerts a strong glucoregulatory incretin through inhibition of gastric emptying, which GIP does not. Thus, GLP‐1 as incretin mimetic may offer unique benefits in terms of weight loss in treatment of type 2 diabetes.
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ISSN:1350-1925
1365-2982
1365-2982
DOI:10.1111/j.1365-2982.2010.01554.x