Carnosine protects pancreatic beta cells and islets against oxidative stress damage

Mol Cell Endocrinol. 2018 Oct 15;474:105-118. doi: 10.1016/j.mce.2018.02.016. Epub 2018 Feb 26.

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.

Keywords: Beta cell line; Carnosine; Diabetes; Oxidative stress; Pancreatic islet transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Biomarkers / metabolism
  • Carnosine / chemistry
  • Carnosine / pharmacology*
  • Cell Line
  • Cell Proliferation / drug effects
  • Cell Shape / drug effects
  • Cell Survival / drug effects
  • Cytoprotection / drug effects*
  • Gene Expression Regulation / drug effects
  • Glucose / pharmacology
  • Humans
  • Hydrogen Peroxide / toxicity
  • Insulin Secretion / drug effects
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / pathology*
  • Mice
  • Nitrous Oxide / metabolism
  • Oxidative Stress / drug effects*
  • Protective Agents / pharmacology
  • Rats
  • Reactive Nitrogen Species / metabolism
  • Reactive Oxygen Species / metabolism
  • Transcription Factor RelA / metabolism
  • Tyrosine / analogs & derivatives
  • Tyrosine / metabolism

Substances

  • Biomarkers
  • Protective Agents
  • Reactive Nitrogen Species
  • Reactive Oxygen Species
  • Transcription Factor RelA
  • 3-nitrotyrosine
  • Tyrosine
  • Carnosine
  • Hydrogen Peroxide
  • Glucose
  • Nitrous Oxide