Effects of GLP-1 and Incretin-based Therapies on Gastrointestinal Motor Function

Overview

Journal Exp Diabetes Res

Specialty Endocrinology

Date 2011 Jul 13

PMID 21747825

Citations 47

Authors

Chinmay S Marathe

Christopher K Rayner

Karen L Jones

Michael Horowitz

Affiliations

Soon will be listed here.

Abstract

Glucagon-like peptide 1 (GLP-1) is a hormone secreted predominantly by the distal small intestine and colon and released in response to enteral nutrient exposure. GLP-1-based therapies are now used widely in the management of type 2 diabetes and have the potential to be effective antiobesity agents. Although widely known as an incretin hormone, there is a growing body of evidence that GLP-1 also acts as an enterogastrone, with profound effects on the gastrointestinal motor system. Moreover, the effects of GLP-1 on gastrointestinal motility appear to be pivotal to its effect of reducing postprandial glycaemic excursions and may, potentially, represent the dominant mechanism. This review summarizes current knowledge of the enterogastrone properties of GLP-1, focusing on its effects on gut motility at physiological and pharmacological concentrations, and the motor actions of incretin-based therapies. While of potential importance, the inhibitory action of GLP-1 on gastric acid secretion is beyond the scope of this paper.

Citing Articles

Gastrointestinal adverse events associated with GLP-1 receptor agonists in metabolic dysfunction-associated steatotic liver disease (MASLD): a systematic review and meta-analysis.

Huang X, Wu M, Huang B, Zhang Y Front Med (Lausanne). 2025; 12:1509947.

PMID: 40051726 PMC: 11882565. DOI: 10.3389/fmed.2025.1509947.

Research progress of GLP-1RAs in the treatment of type 2 diabetes mellitus.

He X, Zhao W, Li P, Zhang Y, Li G, Su H Front Pharmacol. 2025; 15:1483792.

PMID: 39902077 PMC: 11788294. DOI: 10.3389/fphar.2024.1483792.

A Specific Collagen Hydrolysate Improves Postprandial Glucose Tolerance in Normoglycemic and Prediabetic Mice and in a First Proof of Concept Study in Healthy, Normoglycemic and Prediabetic Humans.

Grasset E, Briand F, Virgilio N, Schon C, Wilhelm M, Cudennec B Food Sci Nutr. 2024; 12(11):9607-9620.

PMID: 39619994 PMC: 11606891. DOI: 10.1002/fsn3.4538.

Physiology and Pharmacology of Effects of GLP-1-based Therapies on Gastric, Biliary and Intestinal Motility.

Jalleh R, Marathe C, Rayner C, Jones K, Umapathysivam M, Wu T Endocrinology. 2024; 166(1).

PMID: 39568409 PMC: 11630531. DOI: 10.1210/endocr/bqae155.

Food-induced small bowel obstruction observed in a patient with inappropriate use of semaglutide.

Itoh Y, Tani M, Takahashi R, Yamamoto K Diabetol Int. 2024; 15(4):850-854.

PMID: 39469548 PMC: 11512937. DOI: 10.1007/s13340-024-00751-4.

References

Mari A, Sallas W, He Y, Watson C, Ligueros-Saylan M, Dunning B . Vildagliptin, a dipeptidyl peptidase-IV inhibitor, improves model-assessed beta-cell function in patients with type 2 diabetes. J Clin Endocrinol Metab. 2005; 90(8):4888-94. DOI: 10.1210/jc.2004-2460. View

Hellstrom P, Naslund E, Edholm T, Schmidt P, Kristensen J, Theodorsson E . GLP-1 suppresses gastrointestinal motility and inhibits the migrating motor complex in healthy subjects and patients with irritable bowel syndrome. Neurogastroenterol Motil. 2008; 20(6):649-59. DOI: 10.1111/j.1365-2982.2007.01079.x. View

Edholm T, Degerblad M, Gryback P, Hilsted L, Holst J, Jacobsson H . Differential incretin effects of GIP and GLP-1 on gastric emptying, appetite, and insulin-glucose homeostasis. Neurogastroenterol Motil. 2010; 22(11):1191-200, e315. DOI: 10.1111/j.1365-2982.2010.01554.x. View

Sturm K, Parker B, Wishart J, Feinle-Bisset C, Jones K, Chapman I . Energy intake and appetite are related to antral area in healthy young and older subjects. Am J Clin Nutr. 2004; 80(3):656-67. DOI: 10.1093/ajcn/80.3.656. View

Bouras E, Delgado-Aros S, Camilleri M, Castillo E, Burton D, Thomforde G . SPECT imaging of the stomach: comparison with barostat, and effects of sex, age, body mass index, and fundoplication. Single photon emission computed tomography. Gut. 2002; 51(6):781-6. PMC: 1773479. DOI: 10.1136/gut.51.6.781. View

Vella A, Bock G, Giesler P, Burton D, Serra D, Ligueros Saylan M . Effects of dipeptidyl peptidase-4 inhibition on gastrointestinal function, meal appearance, and glucose metabolism in type 2 diabetes. Diabetes. 2007; 56(5):1475-80. DOI: 10.2337/db07-0136. View

Pilichiewicz A, Chaikomin R, Brennan I, Wishart J, Rayner C, Jones K . Load-dependent effects of duodenal glucose on glycemia, gastrointestinal hormones, antropyloroduodenal motility, and energy intake in healthy men. Am J Physiol Endocrinol Metab. 2007; 293(3):E743-53. DOI: 10.1152/ajpendo.00159.2007. View

Naslund E, Gutniak M, Skogar S, Rossner S, Hellstrom P . Glucagon-like peptide 1 increases the period of postprandial satiety and slows gastric emptying in obese men. Am J Clin Nutr. 1998; 68(3):525-30. DOI: 10.1093/ajcn/68.3.525. View

Rayner C, Samsom M, Jones K, Horowitz M . Relationships of upper gastrointestinal motor and sensory function with glycemic control. Diabetes Care. 2001; 24(2):371-81. DOI: 10.2337/diacare.24.2.371. View

10.

Juhl C, Hollingdal M, Sturis J, Jakobsen G, Agerso H, Veldhuis J . Bedtime administration of NN2211, a long-acting GLP-1 derivative, substantially reduces fasting and postprandial glycemia in type 2 diabetes. Diabetes. 2002; 51(2):424-9. DOI: 10.2337/diabetes.51.2.424. View

11.

Meier J, Kemmeries G, Holst J, Nauck M . Erythromycin antagonizes the deceleration of gastric emptying by glucagon-like peptide 1 and unmasks its insulinotropic effect in healthy subjects. Diabetes. 2005; 54(7):2212-8. DOI: 10.2337/diabetes.54.7.2212. View

12.

Nicolaus M, Brodl J, Linke R, Woerle H, Goke B, Schirra J . Endogenous GLP-1 regulates postprandial glycemia in humans: relative contributions of insulin, glucagon, and gastric emptying. J Clin Endocrinol Metab. 2010; 96(1):229-36. DOI: 10.1210/jc.2010-0841. View

13.

Creutzfeldt W . The [pre-] history of the incretin concept. Regul Pept. 2005; 128(2):87-91. DOI: 10.1016/j.regpep.2004.08.004. View

14.

Jones K, DORAN S, Hveem K, Bartholomeusz F, Morley J, Sun W . Relation between postprandial satiation and antral area in normal subjects. Am J Clin Nutr. 1997; 66(1):127-32. DOI: 10.1093/ajcn/66.1.127. View

15.

Cvetkovic R, Plosker G . Exenatide: a review of its use in patients with type 2 diabetes mellitus (as an adjunct to metformin and/or a sulfonylurea). Drugs. 2007; 67(6):935-54. DOI: 10.2165/00003495-200767060-00008. View

16.

Horowitz M, Harding P, Maddox A, Wishart J, Akkermans L, Chatterton B . Gastric and oesophageal emptying in patients with type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia. 1989; 32(3):151-9. DOI: 10.1007/BF00265086. View

17.

Ma J, Rayner C, Jones K, Horowitz M . Diabetic gastroparesis: diagnosis and management. Drugs. 2009; 69(8):971-86. DOI: 10.2165/00003495-200969080-00003. View

18.

Welch I, Sepple C, Read N . Comparisons of the effects on satiety and eating behaviour of infusion of lipid into the different regions of the small intestine. Gut. 1988; 29(3):306-11. PMC: 1433617. DOI: 10.1136/gut.29.3.306. View

19.

Tolessa T, Gutniak M, Holst J, Efendic S, Hellstrom P . Inhibitory effect of glucagon-like peptide-1 on small bowel motility. Fasting but not fed motility inhibited via nitric oxide independently of insulin and somatostatin. J Clin Invest. 1998; 102(4):764-74. PMC: 508939. DOI: 10.1172/JCI942. View

20.

Kastin A, Akerstrom V, Pan W . Interactions of glucagon-like peptide-1 (GLP-1) with the blood-brain barrier. J Mol Neurosci. 2002; 18(1-2):7-14. DOI: 10.1385/JMN:18:1-2:07. View