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Glucagon-Like Peptide 1 Inhibits Cell Apoptosis and Improves Glucose Responsiveness of Freshly Isolated Human Islets
Abstract
The peptide hormone, glucagon-like peptide 1 (GLP-1), has been shown to increase glucose-dependent insulin secretion, enhance insulin gene transcription, expand islet cell mass, and inhibit beta-cell apoptosis in animal models of diabetes. The aim of the present study was to evaluate whether GLP-1 could improve function and inhibit apoptosis in freshly isolated human islets. Human islets were cultured for 5 d in the presence, or absence, of GLP-1 (10 nm, added every 12 h) and studied for viability and expression of proapoptotic (caspase-3) and antiapoptotic factors (bcl-2) as well as glucose-dependent insulin production. We observed better-preserved three-dimensional islet morphology in the GLP-1-treated islets, compared with controls. Nuclear condensation, a feature of cell apoptosis, was inhibited by GLP-1. The reduction in the number of apoptotic cells in GLP-1-treated islets was particularly evident at d 3 (6.1% apoptotic nuclei in treated cultures vs. 15.5% in controls; P < 0.01) and at d 5 (8.9 vs. 18.9%; P < 0.01). The antiapoptotic effect of GLP-1 was associated with the down-regulation of active caspase-3 (P < 0.001) and the up-regulation of bcl-2 (P < 0.01). The effect of GLP-1 on the intracellular levels of bcl-2 and caspase-3 was observed at the mRNA and protein levels. Intracellular insulin content was markedly enhanced in islets cultured with GLP-1 vs. control (P < 0.001, at d 5), and there was a parallel GLP-1-dependent potentiation of glucose-dependent insulin secretion (P < 0.01 at d 3; P < 0.05 at d 5). Our findings provide evidence that GLP-1 added to freshly isolated human islets preserves morphology and function and inhibits cell apoptosis.
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Metadata
- Authors
- Farilla, L., Bulotta, A., Hirshberg, B., Li Calzi, S., Khoury, N., Noushmehr, H., Bertolotto, C., Di Mario, U., Harlan, D. M., & Perfetti, R.
- Affiliations
- Cedars-Sinai Medical Center (US)
- National Institutes of Health (US)
- Corresponding author
- Perfetti, Riccardo
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2003-12
- Volume
- 144
- Issue
- 12
- Pages
- 5149-5158
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2146333376
- Cited by
- 664
- References
- 34
- Citations by year
- 2026: 6 · 2025: 14 · 2024: 12 · 2023: 11 · 2022: 14 · 2021: 24 · 2020: 15 · 2019: 26 · 2018: 26 · 2017: 23 · 2016: 32 · 2015: 28 · 2014: 36 · 2013: 50 · 2012: 40
- FWCI
- 23.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- glucagon-like peptide-1, beta-cell apoptosis, human pancreatic islets, glucose-dependent insulin secretion, caspase-3, Bcl-2, islet viability, islet morphology, insulin content, islet transplantation, diabetes mellitus
- MeSH terms
- Insulin Secretion, Cell Survival, Cells, Cultured, Fluorescent Antibody Technique, Fluorescent Dyes, Glucagon, Glucose, Humans, Indoles, Insulin, Islets of Langerhans, Peptide Fragments, Protein Precursors, RNA, Messenger, Gene Expression, Apoptosis, Proto-Oncogene Proteins c-bcl-2, Reverse Transcriptase Polymerase Chain Reaction, Caspases, Glucagon-Like Peptide 1, Caspase 3, In Vitro Techniques
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