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.
| Original language | English (US) |
|---|---|
| Journal | Molecular and Cellular Endocrinology |
| DOIs | |
| State | Accepted/In press - Jan 1 2018 |
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Keywords
- Beta cell line
- Carnosine
- Diabetes
- Oxidative stress
- Pancreatic islet transplantation
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Endocrinology
Cite this
Carnosine protects pancreatic beta cells and islets against oxidative stress damage. / Miceli, Vitale; Pampalone, Mariangela; Frazziano, Giovanna; Grasso, Giuseppe; Rizzarelli, Enrico; Ricordi, Camillo; Casu, Anna; Iannolo, Gioacchin; Conaldi, Pier Giulio.
In: Molecular and Cellular Endocrinology, 01.01.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Carnosine protects pancreatic beta cells and islets against oxidative stress damage
AU - Miceli, Vitale
AU - Pampalone, Mariangela
AU - Frazziano, Giovanna
AU - Grasso, Giuseppe
AU - Rizzarelli, Enrico
AU - Ricordi, Camillo
AU - Casu, Anna
AU - Iannolo, Gioacchin
AU - Conaldi, Pier Giulio
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
AB - 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.
KW - Beta cell line
KW - Carnosine
KW - Diabetes
KW - Oxidative stress
KW - Pancreatic islet transplantation
UR - http://www.scopus.com/inward/record.url?scp=85042586527&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85042586527&partnerID=8YFLogxK
U2 - 10.1016/j.mce.2018.02.016
DO - 10.1016/j.mce.2018.02.016
M3 - Article
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
SN - 0303-7207
ER -