Characterization of GLP-1 Effects on β-Cell Function After Meal Ingestion in Humans
Open accessAbstract
OBJECTIVE—Glucagon-like peptide 1 (GLP-1) is an incretin that augments insulin secretion after meal intake and is developed for treatment of type 2 diabetes. As a novel therapeutic agent, characteristics of its β-cell effects are important to establish. Previously, β-cell effects of GLP-1 have been characterized in humans during graded intravenous infusions of glucose, whereas its effects after more physiological stimuli, like meal intake, are not known. RESEARCH DESIGN AND METHODS—Eight women (aged 69 years, fasting glucose 3.7–10.3 mmol/l, BMI 22.4–43.9 kg/m2) who had fasted overnight were served a breakfast (450 kcal) with intravenous infusion of saline or synthetic GLP-1 (0.75 pmol · kg–1 · min–1), and β-cell function was evaluated by estimating the relationship between glucose concentration and insulin secretion (calculated by deconvolution of C-peptide data). RESULTS—GLP-1 markedly augmented insulin secretion, despite lower glucose. Total insulin secretion was 29.7 ± 4.2 nmol/m2 with GLP-1 versus 21.0 ± 1.6 nmol/m2 with saline (P = 0.048). GLP-1 increased the dose-response relationship between glucose concentration and insulin secretion (70 ± 26 with GLP-1 versus 38 ± 16 pmol insulin · min−1 · m2 · mmol−1 glucose · l without, P = 0.037) and augmented the potentiation factor that modulates the dose response (2.71 ± 0.42 with GLP-1 versus 0.97 ± 0.17 without, P = 0.005). The potentiation factor correlated to GLP-1 concentration (r = 0.53, P < 0.001); a 10-fold increase in GLP-1 levels produced a twofold increase in the potentiation factor. These effects of GLP-1 did not correlate with fasting glucose levels or BMI. CONCLUSIONS—Administration of GLP-1 along with ingestion of a meal augments insulin secretion in humans by a dose-dependent potentiation of the dose-response relationship between plasma glucose and insulin secretion.
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- Authors
- Ahrén, B., Holst, J. J., & Mari, A.
- Affiliations
- Department of Medicine, Lund University, Lund, Sweden
- University of Copenhagen (DK)
- National Research Council (IT)
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2003-10-01
- Volume
- 26
- Issue
- 10
- Pages
- 2860-2864
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- OpenAlex
- W1978691530
- Cited by
- 72
- References
- 24
- Citations by year
- 2025: 2 · 2022: 1 · 2021: 2 · 2020: 3 · 2018: 4 · 2017: 4 · 2016: 3 · 2015: 4 · 2014: 3 · 2013: 6 · 2012: 3
- FWCI
- 2.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes Care (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, other-oa)
- Zenodo (CERN European Organization for Nuclear Research)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- glucagon-like peptide-1, beta-cell function, insulin secretion, meal ingestion, incretins, type 2 diabetes, C-peptide, postprandial blood glucose
- MeSH terms
- Insulin Secretion, Aged, Blood Glucose, C-Peptide, Eating, Female, Glucagon, Humans, Insulin, Islets of Langerhans, Peptide Fragments, Protein Precursors, Postprandial Period, Glucagon-Like Peptide 1
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