Carnosine scavenging of glucolipotoxic free radicals enhances insulin secretion and glucose uptake

Cripps, M.J., Hanna, K., Lavilla, C., Sayers, S.R., Caton, P.W., Sims, C., De Girolamo, L., Sale, C. ORCID: 0000-0002-5816-4169 and Turner, M.D. ORCID: 0000-0001-7175-1053, 2017. Carnosine scavenging of glucolipotoxic free radicals enhances insulin secretion and glucose uptake. Scientific Reports, 7 (1), p. 13313. ISSN 2045-2322

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Abstract

The worldwide prevalence of diabetes has risen to 8.5% among adults, which represents a staggering rise in prevalence from 4.7% in 1980. Whilst some treatments work by increasing insulin secretion, over time their effectiveness decreases. We aim to increase insulin secretion by developing strategies that work through mechanisms independent of current treatment options. Isolated CD1 mouse islets, INS-1 pancreatic β-cells, or C2C12 mouse myotubes were incubated in standard tissue culture media, or media supplemented with 28 mM glucose, 200 μM palmitic acid, and 200 μM oleic acid as a cellular model of diabetic glucolipotoxicity. Intracellular reactive species content was assayed using 2′,7′-dichlorofluorescein diacetate dye, inducible nitric oxide synthase levels determined by Western blot, 3-nitrotyrosine and 4-hydrpxnonenal both assayed by ELISA, insulin secretion quantified using ELISA or radioimmunoassay, and glucose uptake determined through 2-deoxy glucose 6 phosphate luminescence. Our data indicate that carnosine, a histidine containing dipeptide available through the diet, is an effective scavenger of each of the aforementioned reactive species. This results in doubling of insulin secretion from isolated mouse islets or INS-1 β-cells. Crucially, carnosine also reverses glucolipotoxic inhibition of insulin secretion and enhances glucose uptake into skeletal muscle cells. Thus, carnosine, or non-hydrolysable carnosine analogs, may represent a new class of therapeutic agent to fight type 2 diabetes.

Item Type: Journal article
Publication Title: Scientific Reports
Creators: Cripps, M.J., Hanna, K., Lavilla, C., Sayers, S.R., Caton, P.W., Sims, C., De Girolamo, L., Sale, C. and Turner, M.D.
Publisher: Nature Publishing Group
Date: 2017
Volume: 7
Number: 1
ISSN: 2045-2322
Identifiers:
NumberType
10.1038/s41598-017-13649-wDOI
13649Publisher Item Identifier
Divisions: Schools > School of Science and Technology
Depositing User: Linda Sullivan
Date Added: 18 Oct 2017 14:22
Last Modified: 18 Oct 2017 14:22
URI: http://irep.ntu.ac.uk/id/eprint/31838

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