Carnosine protects pancreatic beta cells and islets against oxidative stress damage. (15th October 2018)

• Record Type: Journal Article
• Authors: Miceli, Vitale; Pampalone, Mariangela; Frazziano, Giovanna; Grasso, Giuseppe; Rizzarelli, Enrico; Ricordi, Camillo; Casu, Anna; Iannolo, Gioacchin; Conaldi, Pier Giulio
• Is Part Of: Molecular and cellular endocrinology. Volume 474(2018)
• Page Start: 105
• Page End: 118
• Publication Date: 2018-10-15
• Subjects: Beta cell line -- Oxidative stress -- Carnosine -- Diabetes -- Pancreatic islet transplantation; CI CELL index -- D-CA D-carnosine -- L-CA L-carnosine -- NAC N-acetyl-L-cysteine -- DCF-DA 2′, 7-dichlorofluorescein-diacetate -- GSIS glucose stimulated insulin secretion -- H2O2 hydrogen peroxide -- ITx islet transplantation -- NO2 nitrite -- RNS reactive nitrogen species -- ROS reactive oxygen species -- T1DM type 1 diabetes mellitus -- T2DM type 2 diabetes mellitus; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2018.02.016
• Languages: English
• ISSNs: 0303-7207

Abstract

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. Graphical abstract: Highlights: Oxidative stress induces impairment of β-cell vitality and functions. β-cells treated with carnosine improved their resistance to oxidative stress. A similar effect of carnosine was observed in human islets. Carnosine improves insulin production in β-cells damaged by oxidative stress.