PloS one, 2017-08, Vol.12 (8), p.e0181190
2017
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- Autor(en) / Beteiligte
- Titel
- Insulin receptor signaling and glucagon-like peptide 1 effects on pancreatic beta cells
- Ist Teil von
- PloS one, 2017-08, Vol.12 (8), p.e0181190
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2017
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Glucagon-like peptide-1 (GLP-1) is a potent gluco-incretin hormone, which plays a central role on pancreatic beta cell proliferation, survival and insulin secreting activity and whose analogs are used for treating hyperglycemia in type 2 diabetes mellitus. Notably, abnormal insulin signaling affects all the above-mentioned aspects on pancreatic beta cells. The aim of our study was to investigate whether the protective effects of GLP1-1 on beta cells are affected by altered insulin receptor signaling. To this end, several effects of GLP-1 were studied in INS-1E rat beta cells transfected either with an inhibitor of insulin receptor function (i.e., the Ectonucleotide Pyrophosphatase Phosphodiesterase 1, ENPP1), or with insulin receptor small interfering RNA, as well as in control cells. Crucial experiments were carried out also in a second cell line, namely the βTC-1 mouse beta cells. Our data indicate that in insulin secreting beta cells in which either ENPP1 was up-regulated or insulin receptor was down-regulated, GLP-1 positive effects on several pancreatic beta cell activities, including glucose-induced insulin secretion, cell proliferation and cell survival, were strongly reduced. Further studies are needed to understand whether such a scenario occurs also in humans and, if so, if it plays a role of clinical relevance in diabetic patients with poor responsiveness to GLP-1 related treatments.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0181190Titel-ID: cdi_plos_journals_1926447967
- Format
- –
- Schlagworte
- Analogs, Animals, Apoptosis, Apoptosis - drug effects, Beta cells, Biology and Life Sciences, Cell growth, Cell Line, Cell proliferation, Cell Proliferation - drug effects, Cell survival, Diabetes, Diabetes mellitus, Genes, Glucagon, Glucagon-like peptide 1, Glucagon-Like Peptide 1 - pharmacology, Glucose, Glucose - pharmacology, Growth factors, Health aspects, Homeostasis, Hyperglycemia, Immunoglobulins, Insulin, Insulin - metabolism, Insulin receptors, Insulin resistance, Insulin secretion, Insulin-Secreting Cells - cytology, Insulin-Secreting Cells - drug effects, Insulin-Secreting Cells - metabolism, Insulin-Secreting Cells - secretion, Kinases, Medical research, Medicine, Medicine and Health Sciences, Mutagenesis, Site-Directed, Pancreas, Pancreatic beta cells, Penicillin, Peptides, Phosphodiesterase, Phosphoric Diester Hydrolases - genetics, Phosphoric Diester Hydrolases - metabolism, Physical Sciences, Physiological aspects, Proteins, Pyrophosphatase, Pyrophosphatases - genetics, Pyrophosphatases - metabolism, Rats, Receptor, Insulin - antagonists & inhibitors, Receptor, Insulin - genetics, Receptor, Insulin - metabolism, Research and Analysis Methods, Ribonucleic acid, RNA, RNA Interference, RNA, Small Interfering - metabolism, Rodents, Secretion, Signal Transduction - drug effects, siRNA, Staurosporine - pharmacology, Survival