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Exenatide, a Glucagon-like Peptide-1 Receptor Agonist, Acutely Inhibits Intestinal Lipoprotein Production in Healthy Humans
Abstract
Objectives—: Incretin-based therapies for the treatment of type 2 diabetes mellitus improve plasma lipid profiles and postprandial lipemia, but their exact mechanism of action remains unclear. Here, we examined the acute effect of the glucagon-like peptide-1 receptor agonist, exenatide, on intestinal and hepatic triglyceride-rich lipoprotein production and clearance in healthy humans. Methods and Results—: Fifteen normolipidemic, normoglycemic men underwent 2 studies each (SC 10 μg exenatide versus placebo), 4 to 6 weeks apart, in random order, in which triglyceride-rich lipoprotein particle kinetics were examined with a primed, constant infusion of deuterated leucine and analyzed by multicompartmental modeling under pancreatic clamp conditions. A fed state was maintained during each study by infusing a high-fat, mixed macronutrient, liquid formula at a constant rate directly into the duodenum via a nasoduodenal tube. Exenatide significantly suppressed the plasma concentration and production rate of triglyceride-rich lipoprotein-apolipoprotein B-48, but not of triglyceride-rich lipoprotein-apolipoprotein B-100. Conclusions—: These results suggest a possible direct effect of exenatide on intestinal lipoprotein particle production, independent of changes in weight gain and satiety as seen in long-term studies and independent of changes in gastric emptying. This finding expands our understanding of the effects of exenatide in metabolic regulation beyond its primary therapeutic role in regulation of glucose homeostasis. Clinical Trial Registration—: URL: http://www.clinicaltrials.gov , NCT01056549.
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“In one study, osmotic diarrhea occurred 8 h after infusion of GLP-1 peptide (47), and GLP-1RAs have been shown to reduce intestinal uptake of glucose and lipids (48, 49).”
From Safety of Semaglutide (2021) · cites this paper as [49]
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Metadata
- Authors
- Xiao, C., Bandsma, R. H. J., Dash, S., Szeto, L., & Lewis, G. F.
- Affiliations
- University Medical Center Groningen (NL)
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2012-06
- Volume
- 32
- Issue
- 6
- Pages
- 1513-1519
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- OpenAlex
- W2100377339
- Cited by
- 164
- References
- 44
- Citations by year
- 2026: 9 · 2025: 6 · 2024: 9 · 2023: 4 · 2022: 16 · 2021: 15 · 2020: 12 · 2019: 9 · 2018: 15 · 2017: 8 · 2016: 12 · 2015: 20 · 2014: 14 · 2013: 9 · 2012: 5
- FWCI
- 12.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- Canadian Institutes of Health Research
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- exenatide, GLP-1 receptor agonists, triglyceride-rich lipoproteins, apolipoprotein B-48, apolipoprotein B-100, lipoprotein clearance, postprandial lipemia, type 2 diabetes, incretin-based therapy, hepatic lipoprotein production
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Exenatide, Adult, Apolipoproteins B, Blood Glucose, C-Peptide, Glucagon, Humans, Hypoglycemic Agents, Insulin, Intestinal Mucosa, Intestines, Kinetics, Liver, Male, Models, Biological, Ontario, Peptides, Reference Values, Triglycerides, Venoms, Down-Regulation, Receptors, Glucagon, Postprandial Period, Apolipoprotein B-48, Apolipoprotein B-100
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