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Ceramides contained in LDL are elevated in type 2 diabetes and promote inflammation and skeletal muscle insulin resistance

Citation

Boon, J and Hoy, AJ and Stark, R and Brown, RD and Meex, RC and Henstridge, DC and Schenk, S and Meikle, PJ and Horowitz, JF and Kingwell, BA and Bruce, CR and Watt, MJ, Ceramides contained in LDL are elevated in type 2 diabetes and promote inflammation and skeletal muscle insulin resistance, Diabetes, 62, (2) pp. 401-410. ISSN 0012-1797 (2013) [Refereed Article]


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Copyright Statement

Copyright 2012 2012 by the American Diabetes Association. Licensed under Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported (CC BY-NC-ND 3.0) https://creativecommons.org/licenses/by-nc-nd/3.0/

DOI: doi:10.2337/db12-0686

Abstract

Dysregulated lipid metabolism and inflammation are linked to the development of insulin resistance in obesity, and the intracellular accumulation of the sphingolipid ceramide has been implicated in these processes. Here, we explored the role of circulating ceramide on the pathogenesis of insulin resistance. Ceramide transported in LDL is elevated in the plasma of obese patients with type 2 diabetes and correlated with insulin resistance but not with the degree of obesity. Treating cultured myotubes with LDL containing ceramide promoted ceramide accrual in cells and was accompanied by reduced insulin-stimulated glucose uptake, Akt phosphorylation, and GLUT4 translocation compared with LDL deficient in ceramide. LDL-ceramide induced a proinflammatory response in cultured macrophages via toll-like receptor-dependent and -independent mechanisms. Finally, infusing LDL-ceramide into lean mice reduced insulin-stimulated glucose uptake, and this was due to impaired insulin action specifically in skeletal muscle. These newly identified roles of LDL-ceramide suggest that strategies aimed at reducing hepatic ceramide production or reducing ceramide packaging into lipoproteins may improve skeletal muscle insulin action.

Item Details

Item Type:Refereed Article
Keywords:ceramide, glutamate receptor 4, insulin, low density lipoprotein, protein kinase B, toll like receptor, animal cell, animal experiment, animal model, animal tissue, article, cell culture, controlled study, correlational study, enzyme phosphorylation
Research Division:Biological Sciences
Research Group:Biochemistry and cell biology
Research Field:Cell metabolism
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Henstridge, DC (Mr Darren Henstridge)
ID Code:133339
Year Published:2013
Web of Science® Times Cited:145
Deposited By:Health Sciences
Deposited On:2019-06-24
Last Modified:2019-07-22
Downloads:6 View Download Statistics

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