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Cited by 344Diabetes Treatment and ManagementPancreatic function and diabetesDiabetes Management and Research

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Glucagon-like peptide 1 has a physiological role in the control of postprandial glucose in humans: studies with the antagonist exendin 9-39.

Edwards, C M, Todd, J F, Mahmoudi, M, Wang, Z, Wang, R M, Ghatei, M A, Bloom, S R·1999·Diabetes
DOI 10.2337/diabetes.48.1.86
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Abstract

Glucagon-like peptide 1(7-36) amide (GLP-1) is postulated to be the major physiological incretin in humans, but evidence is indirect. We report the first studies examining the physiological role of GLP-1 in the postprandial state in humans using the GLP-1 antagonist exendin 9-39. Exendin 9-39 completely blocked GLP-1-induced glucose-stimulated insulin release from perifused human islets of Langerhans. In healthy fasted volunteers, intravenous infusion of exendin 9-39 at 500 pmol x kg(-1) x min(-1) in the hyperglycemic state abolished the insulinotropic effect of a physiological dose of GLP-1 and fully reversed the glucose-lowering effect of GLP-1. Nine healthy subjects consumed a 150-g oral glucose tolerance test and were infused with 500 pmol x kg(-1) x min(-1) exendin 9-39 or saline. Exendin 9-39 increased the peak postprandial glucose level (exendin 9-39, 8.67 +/- 0.35 vs. saline, 7.67 +/- 0.35 mmol/l, P < or = 0.005) and increased postprandial plasma glucose incremental area under the curve by 35% (exendin 9-39, 152 +/- 19 vs. saline, 113 +/- 16 mmol x min x l(-1), P < or = 0.05). This could be explained as partly secondary to the blockade of glucose-induced suppression of glucagon and maybe also to an increased rate of gastric emptying. Thus, in humans exendin 9-39 acts as an antagonist of GLP-1 both in vitro and in vivo. When infused alone, exendin 9-39 causes a deterioration in postprandial glycemic control, suggesting that GLP-1 may be important for maintenance of normal postprandial glucose homeostasis in humans.

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Metadata

Authors
Edwards, C. M., Todd, J. F., Mahmoudi, M., Wang, Z., Wang, R. M., Ghatei, M. A., & Bloom, S. R.
Affiliations
Hammersmith Hospital (GB)
ORCID
Venue
Diabetes
Publisher
American Diabetes Association
Published
1999-01-01
Volume
48
Issue
1
Pages
86-93
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
DOI
10.2337/diabetes.48.1.86
OpenAlex
W2146581079
Cited by
344
References
0
Citations by year
2026: 4 · 2025: 7 · 2024: 7 · 2023: 10 · 2022: 7 · 2021: 8 · 2020: 9 · 2019: 17 · 2018: 12 · 2017: 12 · 2016: 16 · 2015: 16 · 2014: 13 · 2013: 19 · 2012: 8
FWCI
9.68
Type
journal article
Language
en
Open access
closed
Locations
  • Diabetes (publishedVersion)
  • PubMed (publishedVersion)
Funders
Wellcome Trust
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Keywords
glucagon-like peptide-1, exendin-9-39, incretins, postprandial blood glucose, glucose-stimulated insulin secretion, pancreatic islets, glucagon suppression, gastric emptying, glucose tolerance, insulinotropic effect
MeSH terms
Insulin Secretion, Eating, Glucagon, Glucose, Glucose Tolerance Test, Humans, Insulin, Islets of Langerhans, Peptide Fragments, Protein Precursors, Cytokines, Glucagon-Like Peptide 1, In Vitro Techniques

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