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

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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

Original languageEnglish
Pages (from-to)65-79
Number of pages15
JournalFree Radical Biology and Medicine
Volume175
DOIs
Published1 Nov 2021

Bibliographical note

Funding Information: This study was funded by grant awards from the British Council (grant award numbers: 209524711 ; 279698970 ) and Diabetes UK ( 11/0004417 ). Publisher Copyright: © 2021 Elsevier Inc. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors

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.

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