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

T Edholm; M Degerblad; P Grybäck; L Hilsted; Jens Juul Holst; H Jacobsson; S Efendic; P T Schmidt; P M Hellström

doi:10.1111/j.1365-2982.2010.01554.x

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

T Edholm, M Degerblad, P Grybäck, L Hilsted, Jens Juul Holst, H Jacobsson, S Efendic, P T Schmidt, P M Hellström

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Abstract

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.

Original language	English
Journal	Neurogastroenterology and Motility Online
Volume	22
Issue number	11
Pages (from-to)	1191-200, e315
Number of pages	10
ISSN	1365-2982
DOIs	https://doi.org/10.1111/j.1365-2982.2010.01554.x
Publication status	Published - 1 Nov 2010

Keywords

Adult
Appetite
Blood Glucose
C-Peptide
Cross-Over Studies
Double-Blind Method
Female
Gastric Emptying
Gastric Inhibitory Polypeptide
Ghrelin
Glucagon
Glucagon-Like Peptide 1
Homeostasis
Humans
Hunger
Immunoassay
Incretins
Insulin
Male
Peptide YY
Satiety Response

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1111/j.1365-2982.2010.01554.x

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@article{55e7deaffb2a4a718d4460d3fafbd14d,

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

abstract = "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.",

keywords = "Adult, Appetite, Blood Glucose, C-Peptide, Cross-Over Studies, Double-Blind Method, Female, Gastric Emptying, Gastric Inhibitory Polypeptide, Ghrelin, Glucagon, Glucagon-Like Peptide 1, Homeostasis, Humans, Hunger, Immunoassay, Incretins, Insulin, Male, Peptide YY, Satiety Response",

author = "T Edholm and M Degerblad and P Gryb{\"a}ck and L Hilsted and Holst, {Jens Juul} and H Jacobsson and S Efendic and Schmidt, {P T} and Hellstr{\"o}m, {P M}",

note = "{\textcopyright} 2010 Blackwell Publishing Ltd.",

year = "2010",

month = nov,

day = "1",

doi = "10.1111/j.1365-2982.2010.01554.x",

language = "English",

volume = "22",

pages = "1191--200, e315",

journal = "Neurogastroenterology and Motility Online",

issn = "1365-2982",

publisher = "Wiley-Blackwell",

number = "11",

}

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

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 -

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

Abstract

Keywords

UN SDGs

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