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Differential incretin effects of GIP and GLP-1 on gastric emptying, appetite, and insulin-glucose homeostasis: Incretins, gastric emptying and metabolic control
Open accessAbstract
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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“GLP-1 can slow down gastric emptying through its effects on smooth muscles and the nervous system in the gastrointestinal tract.264,268”
From Glucagon-like peptide-1 receptor: mechanisms and advances in therapy (2024) · cites this paper as [264]
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“GLP-1 suppresses glucagon secretion and has extrahepatic effects such as slowing gastric emptying and suppressing appetite signaling in the brain.16,17”
From Tirzepatide: Clinical review of the twincretin injectable (2023) · cites this paper as [16]
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“Native GIP mimicking postprandial GIP blood levels and GIPRAs did not reveal any relevant effects on GE. 3,[13][14][15]”
From The novel dual glucose‐dependent insulinotropic polypeptide and glucagon‐like peptide‐1 ( GLP ‐1) receptor agonist tirzepatide transiently delays gastric emptying similarly to selective long‐acting GLP ‐1 receptor agonists (2020) · cites this paper as [14]
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Metadata
- Authors
- Edholm, T., Degerblad, M., Grybäck, P., Hilsted, L., Holst, J. J., Jacobsson, H., Efendic, S., Schmidt, P. T., & Hellström, P. M.
- Affiliations
- Karolinska Institutet (SE)
- Rigshospitalet (DK)
- University of Copenhagen (DK)
- Uppsala University (SE)
- Corresponding author
- Hellström, P. M.
- Venue
- Neurogastroenterology & Motility
- Publisher
- Wiley
- Published
- 2010-06-24
- Volume
- 22
- Issue
- 11
- Pages
- 1191-e315
- ISSN
- 1350-1925 (ISSN-L)
- OpenAlex
- W1589619385
- Cited by
- 164
- References
- 51
- Citations by year
- 2026: 10 · 2025: 18 · 2024: 6 · 2023: 7 · 2022: 7 · 2021: 15 · 2020: 5 · 2019: 16 · 2018: 13 · 2017: 13 · 2016: 9 · 2015: 7 · 2014: 9 · 2013: 12 · 2012: 10
- FWCI
- 7.02
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurogastroenterology & Motility (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Stockholms Läns Landsting
- Vetenskapsrådet
- Uppsala Universitet
- Landstinget i Uppsala län
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Keywords
- glucagon-like peptide-1, incretins, gastric emptying, appetite, insulin secretion, glucose homeostasis, postprandial blood glucose, insulinogenic index, satiety, hunger, mixed meal, peptide YY, ghrelin, glucagon, C-peptide, food intake regulation
- MeSH terms
- Adult, Appetite, Blood Glucose, C-Peptide, Double-Blind Method, Female, Gastric Emptying, Gastric Inhibitory Polypeptide, Glucagon, Homeostasis, Humans, Hunger, Immunoassay, Insulin, Male, Satiety Response, Cross-Over Studies, Peptide YY, Glucagon-Like Peptide 1, Ghrelin, Incretins
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