6533b7d8fe1ef96bd126a2d5
RESEARCH PRODUCT
Carnosine protects pancreatic beta cells and islets against oxidative stress damage
Giovanna FrazzianoVitale MiceliGiuseppe GrassoCamillo RicordiMariangela PampalonePier Giulio ConaldiGioacchin IannoloEnrico RizzarelliAnna Casusubject
0301 basic medicineNitrous OxideCarnosineApoptosismedicine.disease_causeBiochemistrychemistry.chemical_compoundMice0302 clinical medicineEndocrinologyInsulin-Secreting CellsInsulin Secretiongeography.geographical_feature_categoryChemistryNitrotyrosineCarnosineDiabetesIsletReactive Nitrogen Speciesmedicine.anatomical_structureBeta cellPancreatic islet transplantationmedicine.medical_specialtyCell SurvivalProtective AgentsCell Line03 medical and health sciencesInternal medicinemedicineAnimalsHumansMolecular BiologyBeta cell lineCell ShapeCell ProliferationSettore MED/04 - Patologia GeneralegeographyPancreatic isletsTranscription Factor RelAHydrogen PeroxideRatsTransplantationOxidative Stress030104 developmental biologyEndocrinologyGlucoseGene Expression RegulationCytoprotectionTyrosinePancreatic islet transplantationReactive Oxygen Species030217 neurology & neurosurgeryOxidative stressBiomarkersdescription
Abstract Islet transplantation is a valid therapeutic option for type 1 diabetes treatment. However, in this procedure one of the major problems is the oxidative stress produced during pancreatic islet isolation. The aim of our study was to evaluate potential protective effects of L-carnosine and its isomer D-carnosine against oxidative stress. We evaluated the carnosine effect on cell growth, cell death, insulin production, and the main markers of oxidative stress in rat and murine stressed beta cell lines as well as in human pancreatic islets. Both isomers clearly inhibited hydrogen peroxide induced cytotoxicity, with a decrease in intracellular reactive oxygen and nitrogen species, prevented hydrogen peroxide induced apoptosis/necrosis, nitrite production, and reduced glucose-induced insulin secretion. In addition, NF-κB expression/translocation and nitrated protein induced in stressed cells was significantly reduced. Furthermore, both isomers improved survival and function, and decreased reactive oxygen and nitrogen species, and nitrite and nitrotyrosine production in human islets cultured for 1, 3, and 7 days. These results seem to indicate that both L and D-carnosine have a significant cytoprotective effect by reducing oxidative stress in beta cell lines and human islets, suggesting their potential use to improve islet survival during the islet transplantation procedure.
year | journal | country | edition | language |
---|---|---|---|---|
2018-10-01 |