Carnosine protects stimulus-secretion coupling through prevention of protein carbonyl adduction events in cells under metabolic stress

Charlie J. Lavilla, Merell P. Billacura, Katie Hanna, David J. Boocock, Clare Coveney, Amanda K. Miles, Gemma A. Foulds, Alice Murphy, Arnold Tan, Laura Jackisch, Sophie R. Sayers, Paul W. Caton, Craig L. Doig, Philip G. McTernan, Sergio L. Colombo, Craig Sale, Mark D. Turner*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Type 2 diabetes is characterised by failure to control glucose homeostasis, with numerous diabetic complications attributable to the resulting exposure of cells and tissues to chronic elevated concentrations of glucose and fatty acids. This, in part, results from formation of advanced glycation and advanced lipidation end-products that are able to modify protein, lipid, or DNA structure, and disrupt normal cellular function. Herein we used mass spectrometry to identify proteins modified by two such adduction events in serum of individuals with obesity, type 2 diabetes, and gestational diabetes, along with similar analyses of human and mouse skeletal muscle cells and mouse pancreatic islets exposed to glucolipotoxic stress. We also report that carnosine, a histidine containing dipeptide, prevented 65–90% of 4-hydroxynonenal and 3-nitrotyrosine adduction events, and that this in turn preserved mitochondrial function and protected stimulus-secretion coupling in cells exposed to metabolic stress. Carnosine therefore offers significant therapeutic potential against metabolic diseases.

Original languageEnglish
Pages (from-to)65-79
Number of pages15
JournalFree Radical Biology and Medicine
Volume175
DOIs
Publication statusPublished - 1 Nov 2021

Keywords

  • Gestational diabetes
  • Glucolipotoxicity
  • GLUT4 translocation
  • Obesity
  • Reactive species scavenging
  • Type 2 diabetes

Fingerprint

Dive into the research topics of 'Carnosine protects stimulus-secretion coupling through prevention of protein carbonyl adduction events in cells under metabolic stress'. Together they form a unique fingerprint.

Cite this