NADPH oxidase NOX2 defines a new antagonistic role for reactive oxygen species and cAMP/PKA in the regulation of insulin secretion
| العنوان: | NADPH oxidase NOX2 defines a new antagonistic role for reactive oxygen species and cAMP/PKA in the regulation of insulin secretion |
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| المؤلفون: | Thierry Brun, Youssef Daali, Karl-Heinz Krause, Xiao-Juan Ma, Christine Deffert-Delbouille, Ning Li, Pierre Maechler, Bin Li, Zahia Mahiout |
| المصدر: | Diabetes Diabetes, Vol. 61, No 11 (2012) pp. 2842-50 |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Endocrinology, Diabetes and Metabolism, Cyclic AMP/agonists/antagonists & inhibitors/metabolism, Second Messenger Systems, Tissue Culture Techniques, chemistry.chemical_compound, Mice, 0302 clinical medicine, Glucagon-Like Peptide 1/metabolism, Glucagon-Like Peptide 1, Insulin-Secreting Cells, Insulin Secretion, Cyclic AMP, Insulin, RNA, Small Interfering, Cellular localization, Cells, Cultured, chemistry.chemical_classification, Mice, Knockout, 0303 health sciences, NADPH Oxidase/antagonists & inhibitors/genetics/metabolism, NADPH oxidase, Membrane Glycoproteins, Superoxide, Cell biology, Isoenzymes, medicine.anatomical_structure, Knockout mouse, NADPH Oxidase 2, cardiovascular system, hormones, hormone substitutes, and hormone antagonists, circulatory and respiratory physiology, medicine.medical_specialty, endocrine system, Insulin-Secreting Cells/cytology/drug effects/metabolism/secretion, Islets of Langerhans/cytology/drug effects/metabolism/secretion, 030209 endocrinology & metabolism, Biology, 03 medical and health sciences, Islets of Langerhans, Reactive Oxygen Species/metabolism, Second Messenger Systems/drug effects, Internal medicine, Lysosome, Secretory Vesicles/drug effects/metabolism, Internal Medicine, medicine, Animals, Humans, Gene Silencing, ddc:612, Protein kinase A, Protein Kinase Inhibitors, 030304 developmental biology, Insulin/secretion, Reactive oxygen species, Membrane Glycoproteins/antagonists & inhibitors/genetics/metabolism, urogenital system, Pancreatic islets, Secretory Vesicles, NADPH Oxidases, Cyclic AMP-Dependent Protein Kinases, Mice, Inbred C57BL, Endocrinology, chemistry, Islet Studies, Protein Kinase Inhibitors/pharmacology, Isoenzymes/antagonists & inhibitors/genetics/metabolism, biology.protein, Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors/metabolism, Reactive Oxygen Species |
| الوصف: | In insulin-secreting cells, expression of NADPH oxidase (NOX), a potent source of ROS, has been reported, along with controversial findings regarding its function. Here, the role of NOXs was investigated: first by expression and cellular localization in mouse and human pancreatic islets, and then by functional studies in islets isolated from Nox isoform–specific knockout mice. Both human and mouse β-cells express NOX, in particular NOX2. With use of Nox isoform–specific knockout mice, functional analysis revealed Nox2 as the predominant isoform. In human islets, NOX2 colocalized with both insulin granules and endosome/lysosome membranes. Nox2-deficient islets stimulated with 22.8 mmol/L glucose exhibited potentiation of insulin release compared with controls, an effect confirmed with in vitro knockdown of Nox2. The enhanced secretory function in Nox2-deficient islets was associated with both lower superoxide levels and elevated cAMP concentrations. In control islets, GLP-1 and other cAMP inducers suppressed glucose-induced ROS production similarly to Nox2 deficiency. Inhibiting cAMP-dependent protein kinase reduced the secretory response in Nox2-null islets, although not in control islets. This study ascribes a new role for NOX2 in pancreatic β-cells as negative modulator of the secretory response, reducing cAMP/PKA signaling secondary to ROS generation. Results also show reciprocal inhibition between the cAMP/PKA pathway and ROS. |
| تدمد: | 1939-327X 0012-1797 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3979bc5072986dd8b05dc4e9ca29b1f1 https://pubmed.ncbi.nlm.nih.gov/22933115 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....3979bc5072986dd8b05dc4e9ca29b1f1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1939327X 00121797 |
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