The glucagon-like peptide-1 metabolite GLP-1-(9–36) amide reduces postprandial glycemia independently of gastric emptying and insulin secretion in humans
Abstract
Glucagon-like peptide 1 (GLP-1) lowers glycemia by modulating gastric emptying and endocrine pancreatic secretion. Rapidly after its secretion, GLP-1-(7–36) amide is degraded to the metabolite GLP-1-(9–36) amide. The effects of GLP-1-(9–36) amide in humans are less well characterized. Fourteen healthy volunteers were studied with intravenous infusion of GLP-1-(7–36) amide, GLP-1-(9–36) amide, or placebo over 390 min. After 30 min, a solid test meal was served, and gastric emptying was assessed. Blood was drawn for GLP-1 (total and intact), glucose, insulin, C-peptide, and glucagon measurements. Administration of GLP-1-(7–36) amide and GLP-1-(9–36) amide significantly raised total GLP-1 plasma levels. Plasma concentrations of intact GLP-1 increased to 21 ± 5 pmol/l during the infusion of GLP-1-(7–36) amide but remained unchanged during GLP-1-(9–36) amide infusion [5 ± 3 pmol/l; P < 0.001 vs. GLP-1-(7–36) amide administration]. GLP-1-(7–36) amide reduced fasting and postprandial glucose concentrations ( P < 0.001) and delayed gastric emptying ( P < 0.001). The GLP-1 metabolite had no influence on insulin or C-peptide concentrations. Glucagon levels were lowered by GLP-1-(7–36) amide but not by GLP-1-(9–36) amide. However, the postprandial rise in glycemia was reduced significantly (by ∼6 mg/dl) by GLP-1-(9–36) amide ( P < 0.05). In contrast, gastric emptying was completely unaffected by the GLP-1 metabolite. The GLP-1 metabolite lowers postprandial glycemia independently of changes in insulin and glucagon secretion or in the rate of gastric emptying. Most likely, this is because of direct effects on glucose disposal. However, the glucose-lowering potential of GLP-1-(9–36) amide appears to be small compared with that of intact GLP-1-(7–36) amide.
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Infusion of GLP-1 (7-36 amide) at a rate comparable to our studies increased plasma insulin concentrations on average from ∼8 to 15 mU/l.
“Infusion of GLP-1 (7-36 amide) at a rate comparable to our studies increased plasma insulin concentrations on average from ∼8 to 15 mU/l (24), which is comparable to the insulin concentrations (i.e., 10 to 25 mU/l), which increased MSNA (i.e., from 16 to 25 bursts/min) during insulin euglycemic clamp infusion (17).”
From Effects of glucagon-like peptide-1, yohimbine, and nitrergic modulation on sympathetic and parasympathetic activity in humans (2008) · cites this paper as [24]
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References 36 · Cited by 104
- Authors
- Meier, J. J., Gethmann, A., Nauck, M. A., Götze, O., Schmitz, F., Deacon, C. F., Gallwitz, B., Schmidt, W. E., & Holst, J. J.
- Affiliations
- St. Josef-Hospital (DE)
- ORCID
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2006-06
- Volume
- 290
- Issue
- 6
- Pages
- E1118-E1123
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- OpenAlex
- W2130083450
- Cited by
- 104
- References
- 36
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 4 · 2020: 3 · 2019: 7 · 2017: 5 · 2016: 5 · 2015: 3 · 2014: 7 · 2013: 5 · 2012: 6
- FWCI
- 6.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- glucagon-like peptide-1, GLP-1(7-36)amide, postprandial blood glucose, gastric emptying, insulin secretion, glucagon secretion, glucose disposal, glucose homeostasis, C-peptide, pancreatic islets
- MeSH terms
- Adult, Blood Glucose, C-Peptide, Gastric Emptying, Humans, Hypoglycemia, Insulin, Male, Peptides, Time Factors, Lipid Metabolism, Glucagon-Like Peptide 1
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