ArticlePloS one2014
Chronic exposure to GLP-1 increases GLP-1 synthesis and release in a pancreatic alpha cell line (α-TC1): evidence of a direct effect of GLP-1 on pancreatic alpha cells.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- Metabolic state determines the brain and direct islet effects of liraglutide on enhanced insulin secretion.Diabetologia · 2026Article
- The Role of the α Cell in the Pathogenesis of Diabetes: A World beyond the Mirror.International journal of molecular sciences · 2021Review
- Betacellulin-Induced α-Cell Proliferation Is Mediated by ErbB3 and ErbB4, and May Contribute to β-Cell Regeneration.Frontiers in cell and developmental biology · 2020Article
- Drug Delivery System in the Treatment of Diabetes Mellitus.Frontiers in bioengineering and biotechnology · 2020Review
- Impaired glucagon suppression and reduced insulin sensitivity in subjects with prediabetes undergoing atorvastatin therapy.European journal of endocrinology · 2019Article
- Mineralocorticoid Receptor May Regulate Glucose Homeostasis through the Induction of Interleukin-6 and Glucagon-Like peptide-1 in Pancreatic Islets.Journal of clinical medicine · 2019Article
- Nonclassical Islet Peptides: Pancreatic and Extrapancreatic Actions.Clinical medicine insights. Endocrinology and diabetes · 2019Review
- GLP-1 Receptor in Pancreatic α-Cells Regulates Glucagon Secretion in a Glucose-Dependent Bidirectional Manner.Diabetes · 2019Article
- Article
- Brain GLP-1/IGF-1 Signaling and Autophagy Mediate Exendin-4 Protection Against Apoptosis in Type 2 Diabetic Rats.Molecular neurobiology · 2018Article
- Pancreatic alpha cells in diabetic rats express active GLP-1 receptor: Endosomal co-localization of GLP-1/GLP-1R complex functioning through intra-islet paracrine mechanism.Scientific reports · 2018Article
- Pleiotropic Effects of GLP-1 and Analogs on Cell Signaling, Metabolism, and Function.Frontiers in endocrinology · 2018Review
- Dissecting the Physiology and Pathophysiology of Glucagon-Like Peptide-1.Frontiers in endocrinology · 2018Review
- Plasticity in the Glucagon Interactome Reveals Novel Proteins That Regulate Glucagon Secretion in α-TC1-6 Cells.Frontiers in endocrinology · 2018Article
- Alpha TC1 and Beta-TC-6 genomic profiling uncovers both shared and distinct transcriptional regulatory features with their primary islet counterparts.Scientific reports · 2017Article
- Atorvastatin but Not Pravastatin Impairs Mitochondrial Function in Human Pancreatic Islets and Rat β-Cells. Direct Effect of Oxidative Stress.Scientific reports · 2017Article
- Article
- Abnormal CFTR Affects Glucagon Production by Islet α Cells in Cystic Fibrosis and Polycystic Ovarian Syndrome.Frontiers in physiology · 2017Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisIncretin therapies, which are used to treat diabetic patients, cause a chronic supra-physiological increase in GLP-1 circulating levels. It is still unclear how the resulting high hormone concentrations may affect pancreatic alpha cells. The present study was designed to investigate the effects of chronic exposure to high GLP-1 levels on a cultured pancreatic alpha cell line.
methodsα-TC1-6 cell line was cultured in the presence or absence of GLP-1 (100 nmol/l) for up to 72 h. In our model GLP-1 receptor (GLP-1R) was measured. After the cells were exposed to GLP-1 the levels of glucagon secretion were measured. Because GLP-1 acts on intracellular cAMP production, the function of GLP-1R was studied. We also investigated the effects of chronic GLP-1 exposure on the cAMP/MAPK pathway, Pax6 levels, the expression of prohormone convertases (PCs), glucagon gene (Gcg) and protein expression, glucagon and GLP-1 production.
resultsIn our model, we were able to detect GLP-1R. After GLP-1 exposure we found a reduction in glucagon secretion. During further investigation of the function of GLP-1R, we found an activation of the cAMP/MAPK/Pax6 pathway and an increase of Gcg gene and protein expression. Furthermore we observed a significant increase in PC1/3 protein expression, GLP-1 intracellular content and GLP-1 secretion. CONCLUSIONS/
interpretationOur data indicate that the chronic exposure of pancreatic alpha cells to GLP-1 increases the ability of these cells to produce and release GLP-1. This phenomenon occurs through the stimulation of the transcription factor Pax6 and the increased expression of the protein convertase PC1/3.
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