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Differential incretin effects of GIP and GLP‐1 on gastric emptying, appetite, and insulin‐glucose homeostasis
Author(s) -
Edholm T.,
Degerblad M.,
Grybäck P.,
Hilsted L.,
Holst J. J.,
Jacobsson H.,
Efendic S.,
Schmidt P. T.,
Hellström P. M.
Publication year - 2010
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/j.1365-2982.2010.01554.x
Subject(s) - medicine , postprandial , incretin , gastric emptying , endocrinology , gastric inhibitory polypeptide , glucagon like peptide 1 , peptide yy , insulin , crossover study , glucose homeostasis , appetite , glucagon , type 2 diabetes , ghrelin , diabetes mellitus , hormone , insulin resistance , neuropeptide , stomach , receptor , neuropeptide y receptor , placebo , alternative medicine , pathology
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.