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

TY - JOUR

T1 - Differential incretin effects of GIP and GLP-1 on gastric emptying, appetite, and insulin-glucose homeostasis

AU - Edholm, T

AU - Degerblad, M

AU - Grybäck, P

AU - Hilsted, L

AU - Holst, Jens Juul

AU - Jacobsson, H

AU - Efendic, S

AU - Schmidt, P T

AU - Hellström, P M

N1 - © 2010 Blackwell Publishing Ltd.

PY - 2010/11/1

Y1 - 2010/11/1

N2 - 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.

AB - 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.

KW - Adult

KW - Appetite

KW - Blood Glucose

KW - C-Peptide

KW - Cross-Over Studies

KW - Double-Blind Method

KW - Female

KW - Gastric Emptying

KW - Gastric Inhibitory Polypeptide

KW - Ghrelin

KW - Glucagon

KW - Glucagon-Like Peptide 1

KW - Homeostasis

KW - Humans

KW - Hunger

KW - Immunoassay

KW - Incretins

KW - Insulin

KW - Male

KW - Peptide YY

KW - Satiety Response

U2 - 10.1111/j.1365-2982.2010.01554.x

DO - 10.1111/j.1365-2982.2010.01554.x

M3 - Journal article

C2 - 20584260

SN - 1365-2982

VL - 22

SP - 1191-200, e315

JO - Neurogastroenterology and Motility Online

JF - Neurogastroenterology and Motility Online

IS - 11

ER -