Cited by 669Pancreatic function and diabetesDiabetes Treatment and ManagementDiabetes and associated disorders

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Glucagon-Like Peptide 1 Inhibits Cell Apoptosis and Improves Glucose Responsiveness of Freshly Isolated Human Islets

Farilla, Loredana, Bulotta, Angela, Hirshberg, Boaz, Li Calzi, Sergio, Khoury, Nasif, Noushmehr, Houtan, Bertolotto, Cristina, Di Mario, Umberto, Harlan, David M., Perfetti, Riccardo·2003·Endocrinology

DOI 10.1210/en.2003-0323

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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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Dipeptidyl Peptidase‐4 Inhibitors for the Treatment of Type 2 Diabetes Mellitus
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Background

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
ORCID: Hirshberg, Boaz
Noushmehr, Houtan
Harlan, David M.
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
DOI: 10.1210/en.2003-0323
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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Glucagon-Like Peptide 1 Inhibits Cell Apoptosis and Improves Glucose Responsiveness of Freshly Isolated Human Islets

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