133339 - Ceramides contained in LDL are elevated in type 2 diabetes and promote inflammation and skeletal muscle insulin resistance.pdf (1.33 MB)
Ceramides contained in LDL are elevated in type 2 diabetes and promote inflammation and skeletal muscle insulin resistance
journal contribution
posted on 2023-05-20, 04:43 authored by Boon, J, Hoy, AJ, Stark, R, Brown, RD, Meex, RC, Darren HenstridgeDarren Henstridge, Schenk, S, Meikle, PJ, Horowitz, JF, Kingwell, BA, Bruce, CR, Watt, MJDysregulated 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.
History
Publication title
DiabetesVolume
62Pagination
401-410ISSN
0012-1797Department/School
School of Health SciencesPublisher
Amer Diabetes AssocPlace of publication
1701 N Beauregard St, Alexandria, USA, Va, 22311-1717Rights 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/Repository Status
- Open