Glucagon-Like Peptide-1 Triggers Protective Pathways in Pancreatic Beta-Cells Exposed to Glycated Serum
Advanced glycation end products (AGEs) might play a pathophysiological role in the development of diabetes and its complications. AGEs negatively affect pancreatic beta-cell function and the expression of transcriptional factors regulating insulin gene. Glucagon-like peptide-1 (GLP-1), an incretin h...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2013-01-01
|
| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2013/317120 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832561634844868608 |
|---|---|
| author | Alessandra Puddu Roberta Sanguineti Arianna Durante Alessio Nencioni François Mach Fabrizio Montecucco Giorgio L. Viviani |
| author_facet | Alessandra Puddu Roberta Sanguineti Arianna Durante Alessio Nencioni François Mach Fabrizio Montecucco Giorgio L. Viviani |
| author_sort | Alessandra Puddu |
| collection | DOAJ |
| description | Advanced glycation end products (AGEs) might play a pathophysiological role in the development of diabetes and its complications. AGEs negatively affect pancreatic beta-cell function and the expression of transcriptional factors regulating insulin gene. Glucagon-like peptide-1 (GLP-1), an incretin hormone that regulates glucose homeostasis, might counteract the harmful effects of AGEs on the beta cells in culture. The aim of this study was to identify the intracellular mechanisms underlying GLP-1-mediated protection from AGE-induced detrimental activities in pancreatic beta cells. HIT-T15 cells were cultured for 5 days with glycated serum (GS, consisting in a pool of AGEs), in the presence or absence of 10 nmol/L GLP-1. After evaluation of oxidative stress, we determined the expression and subcellular localization of proteins involved in maintaining redox balance and insulin gene expression, such as nuclear factor erythroid-derived 2 (Nrf2), glutathione reductase, PDX-1, and MafA. Then, we investigated proinsulin production. The results showed that GS increased oxidative stress, reduced protein expression of all investigated factors through proteasome activation, and decreased proinsulin content. Furthermore, GS reduced ability of PDX-1 and MafA to bind DNA. Coincubation with GLP-1 reversed these GS-mediated detrimental effects. In conclusion, GLP-1, protecting cells against oxidants, triggers protective intercellular pathways in HIT-T15 cells exposed to GS. |
| format | Article |
| id | doaj-art-51f6222f4d20432c809e47936d207a4f |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-51f6222f4d20432c809e47936d207a4f2025-02-03T01:24:30ZengWileyMediators of Inflammation0962-93511466-18612013-01-01201310.1155/2013/317120317120Glucagon-Like Peptide-1 Triggers Protective Pathways in Pancreatic Beta-Cells Exposed to Glycated SerumAlessandra Puddu0Roberta Sanguineti1Arianna Durante2Alessio Nencioni3François Mach4Fabrizio Montecucco5Giorgio L. Viviani6Department of Internal Medicine and Medical Specialties, University of Genova, 6 Viale Benedetto XV, 16132 Genova, ItalyDepartment of Internal Medicine and Medical Specialties, University of Genova, 6 Viale Benedetto XV, 16132 Genova, ItalyDepartment of Internal Medicine and Medical Specialties, University of Genova, 6 Viale Benedetto XV, 16132 Genova, ItalyDepartment of Internal Medicine and Medical Specialties, University of Genova, 6 Viale Benedetto XV, 16132 Genova, ItalyDivision of Cardiology, Geneva University Hospitals, Faculty of Medicine, Foundation for Medical Researches, 64 Avenue de la Roseraie, 1211 Geneva, SwitzerlandDepartment of Internal Medicine and Medical Specialties, University of Genova, 6 Viale Benedetto XV, 16132 Genova, ItalyDepartment of Internal Medicine and Medical Specialties, University of Genova, 6 Viale Benedetto XV, 16132 Genova, ItalyAdvanced glycation end products (AGEs) might play a pathophysiological role in the development of diabetes and its complications. AGEs negatively affect pancreatic beta-cell function and the expression of transcriptional factors regulating insulin gene. Glucagon-like peptide-1 (GLP-1), an incretin hormone that regulates glucose homeostasis, might counteract the harmful effects of AGEs on the beta cells in culture. The aim of this study was to identify the intracellular mechanisms underlying GLP-1-mediated protection from AGE-induced detrimental activities in pancreatic beta cells. HIT-T15 cells were cultured for 5 days with glycated serum (GS, consisting in a pool of AGEs), in the presence or absence of 10 nmol/L GLP-1. After evaluation of oxidative stress, we determined the expression and subcellular localization of proteins involved in maintaining redox balance and insulin gene expression, such as nuclear factor erythroid-derived 2 (Nrf2), glutathione reductase, PDX-1, and MafA. Then, we investigated proinsulin production. The results showed that GS increased oxidative stress, reduced protein expression of all investigated factors through proteasome activation, and decreased proinsulin content. Furthermore, GS reduced ability of PDX-1 and MafA to bind DNA. Coincubation with GLP-1 reversed these GS-mediated detrimental effects. In conclusion, GLP-1, protecting cells against oxidants, triggers protective intercellular pathways in HIT-T15 cells exposed to GS.http://dx.doi.org/10.1155/2013/317120 |
| spellingShingle | Alessandra Puddu Roberta Sanguineti Arianna Durante Alessio Nencioni François Mach Fabrizio Montecucco Giorgio L. Viviani Glucagon-Like Peptide-1 Triggers Protective Pathways in Pancreatic Beta-Cells Exposed to Glycated Serum Mediators of Inflammation |
| title | Glucagon-Like Peptide-1 Triggers Protective Pathways in Pancreatic Beta-Cells Exposed to Glycated Serum |
| title_full | Glucagon-Like Peptide-1 Triggers Protective Pathways in Pancreatic Beta-Cells Exposed to Glycated Serum |
| title_fullStr | Glucagon-Like Peptide-1 Triggers Protective Pathways in Pancreatic Beta-Cells Exposed to Glycated Serum |
| title_full_unstemmed | Glucagon-Like Peptide-1 Triggers Protective Pathways in Pancreatic Beta-Cells Exposed to Glycated Serum |
| title_short | Glucagon-Like Peptide-1 Triggers Protective Pathways in Pancreatic Beta-Cells Exposed to Glycated Serum |
| title_sort | glucagon like peptide 1 triggers protective pathways in pancreatic beta cells exposed to glycated serum |
| url | http://dx.doi.org/10.1155/2013/317120 |
| work_keys_str_mv | AT alessandrapuddu glucagonlikepeptide1triggersprotectivepathwaysinpancreaticbetacellsexposedtoglycatedserum AT robertasanguineti glucagonlikepeptide1triggersprotectivepathwaysinpancreaticbetacellsexposedtoglycatedserum AT ariannadurante glucagonlikepeptide1triggersprotectivepathwaysinpancreaticbetacellsexposedtoglycatedserum AT alessionencioni glucagonlikepeptide1triggersprotectivepathwaysinpancreaticbetacellsexposedtoglycatedserum AT francoismach glucagonlikepeptide1triggersprotectivepathwaysinpancreaticbetacellsexposedtoglycatedserum AT fabriziomontecucco glucagonlikepeptide1triggersprotectivepathwaysinpancreaticbetacellsexposedtoglycatedserum AT giorgiolviviani glucagonlikepeptide1triggersprotectivepathwaysinpancreaticbetacellsexposedtoglycatedserum |