Differential incretin effects of GIP and GLP-1 on gastric emptying, appetite, and insulin-glucose homeostasis: Incretins, gastric emptying and metabolic control
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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.
“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]
The Gastric emptying results report that GLP-1 slowed gastric emptying, and the Discussion suggests changes in antral, fundic and pyloric motility as the basis. The paper does not establish that effects on smooth muscle and the gastrointestinal nervous system jointly mediate this slowing; a nervous-system mechanism appears only in the title of a cited rat study (Reference 13). Page numbers are unavailable in our copy. (LLM, conf=0.84)
Experimental — accuracy not yet measuredGLP-1 suppresses glucagon secretion and has extrahepatic effects such as slowing gastric emptying and suppressing appetite signaling in the brain.
“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]
The Discussion reports that GLP-1 slowed gastric emptying and that the delay reduced plasma pancreatic glucagon levels; it does not establish direct suppression of glucagon secretion. It also reports reduced hunger and desire to eat, but explicitly says the study cannot determine whether these effects involve the central nervous system. Page numbers are not available in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measured
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- 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 › Surgery › 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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