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Differential incretin effects of GIP and GLP-1 on gastric emptying, appetite, and insulin-glucose homeostasis
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2010 (English)In: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 22, no 11, 1191-e315 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2010. Vol. 22, no 11, 1191-e315 p.
Keyword [en]
appetite, gastrointestinal hormones, glucagon-like peptide, glucose metabolism, insulin signaling
National Category
Gastroenterology and Hepatology
Research subject
Medical Science
Identifiers
URN: urn:nbn:se:uu:diva-134345DOI: 10.1111/j.1365-2982.2010.01554.xISI: 000282692500008OAI: oai:DiVA.org:uu-134345DiVA: diva2:372436
Available from: 2010-11-25 Created: 2010-11-24 Last updated: 2017-12-12Bibliographically approved

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Hellström, Per M.

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