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Effects of GLP-1 and Its Analogs on Gastric Physiology in Diabetes Mellitus and Obesity.
Adv Exp Med Biol. 2020 Feb 20 [Online ahead of print]AE

Abstract

The processing of proglucagon in intestinal L cells results in the formation of glucagon, GLP-1, and GLP-2. The GLP-1 molecule becomes active through the effect of proconvertase 1, and it is inactivated by dipeptidyl peptidase IV (DPP-IV), so that the half-life of endogenous GLP-1 is 2-3 min. GLP-1 stimulates insulin secretion from β cells in the islets of Langerhans. Human studies show that infusion of GLP-1 results in slowing of gastric emptying and increased fasting and postprandial gastric volumes. Retardation of gastric emptying reduces postprandial glycemia. Exendin-4 is a peptide agonist of the GLP-1 receptor that promotes insulin secretion. Chemical modifications of exendin-4 and GLP-1 molecules have been accomplished to prolong the half-life of GLP-1 agonists or analogs. This chapter reviews the effects of GLP-1-related drugs used in treatment of diabetes or obesity on gastric motor functions, chiefly gastric emptying. The literature shows that diverse methods have been used to measure effects of the GLP-1-related drugs on gastric emptying, with most studies using the acetaminophen absorption test which essentially measures gastric emptying of liquids during the first hour and capacity to absorb the drug over 4-6 h, expressed as AUC. The most valid measurements by scintigraphy (solids or liquids) and acetaminophen absorption at 30 or 60 min show that GLP-1-related drugs used in diabetes or obesity retard gastric emptying, and this is associated with reduced glycemia and variable effects on food intake and appetite. GLP-1 agonists and analogs are integral to the management of patients with type 2 diabetes mellitus and obesity. The effects on gastric emptying are reduced with long-acting preparations or long-term use of short-acting preparations as a result of tachyphylaxis. The dual agonists targeting GLP-1 and another receptor (GIP) do not retard gastric emptying, based on reports to date. In summary, GLP-1 agonists and analogs are integral to the management of patients with type 2 diabetes mellitus and obesity, and their effects are mediated, at least in part, by retardation of gastric emptying.

Authors+Show Affiliations

Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA. camilleri.michael@mayo.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32077010

Citation

Maselli, Daniel B., and Michael Camilleri. "Effects of GLP-1 and Its Analogs On Gastric Physiology in Diabetes Mellitus and Obesity." Advances in Experimental Medicine and Biology, 2020.
Maselli DB, Camilleri M. Effects of GLP-1 and Its Analogs on Gastric Physiology in Diabetes Mellitus and Obesity. Adv Exp Med Biol. 2020.
Maselli, D. B., & Camilleri, M. (2020). Effects of GLP-1 and Its Analogs on Gastric Physiology in Diabetes Mellitus and Obesity. Advances in Experimental Medicine and Biology. https://doi.org/10.1007/5584_2020_496
Maselli DB, Camilleri M. Effects of GLP-1 and Its Analogs On Gastric Physiology in Diabetes Mellitus and Obesity. Adv Exp Med Biol. 2020 Feb 20; PubMed PMID: 32077010.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of GLP-1 and Its Analogs on Gastric Physiology in Diabetes Mellitus and Obesity. AU - Maselli,Daniel B, AU - Camilleri,Michael, Y1 - 2020/02/20/ PY - 2020/2/21/entrez KW - Accommodation KW - Albiglutide KW - Appetite KW - Dulaglutide KW - Emptying KW - Exenatide KW - Liraglutide KW - Lixisenatide KW - Semaglutide JF - Advances in experimental medicine and biology JO - Adv. Exp. Med. Biol. N2 - The processing of proglucagon in intestinal L cells results in the formation of glucagon, GLP-1, and GLP-2. The GLP-1 molecule becomes active through the effect of proconvertase 1, and it is inactivated by dipeptidyl peptidase IV (DPP-IV), so that the half-life of endogenous GLP-1 is 2-3 min. GLP-1 stimulates insulin secretion from β cells in the islets of Langerhans. Human studies show that infusion of GLP-1 results in slowing of gastric emptying and increased fasting and postprandial gastric volumes. Retardation of gastric emptying reduces postprandial glycemia. Exendin-4 is a peptide agonist of the GLP-1 receptor that promotes insulin secretion. Chemical modifications of exendin-4 and GLP-1 molecules have been accomplished to prolong the half-life of GLP-1 agonists or analogs. This chapter reviews the effects of GLP-1-related drugs used in treatment of diabetes or obesity on gastric motor functions, chiefly gastric emptying. The literature shows that diverse methods have been used to measure effects of the GLP-1-related drugs on gastric emptying, with most studies using the acetaminophen absorption test which essentially measures gastric emptying of liquids during the first hour and capacity to absorb the drug over 4-6 h, expressed as AUC. The most valid measurements by scintigraphy (solids or liquids) and acetaminophen absorption at 30 or 60 min show that GLP-1-related drugs used in diabetes or obesity retard gastric emptying, and this is associated with reduced glycemia and variable effects on food intake and appetite. GLP-1 agonists and analogs are integral to the management of patients with type 2 diabetes mellitus and obesity. The effects on gastric emptying are reduced with long-acting preparations or long-term use of short-acting preparations as a result of tachyphylaxis. The dual agonists targeting GLP-1 and another receptor (GIP) do not retard gastric emptying, based on reports to date. In summary, GLP-1 agonists and analogs are integral to the management of patients with type 2 diabetes mellitus and obesity, and their effects are mediated, at least in part, by retardation of gastric emptying. SN - 0065-2598 UR - https://www.unboundmedicine.com/medline/citation/32077010/Effects_of_GLP-1_and_Its_Analogs_on_Gastric_Physiology_in_Diabetes_Mellitus_and_Obesity L2 - https://dx.doi.org/10.1007/5584_2020_496 DB - PRIME DP - Unbound Medicine ER -
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