Research ArticleMetabolism

The glucocorticoid-Angptl4-ceramide axis induces insulin resistance through PP2A and PKCζ

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Sci. Signal.  25 Jul 2017:
Vol. 10, Issue 489, eaai7905
DOI: 10.1126/scisignal.aai7905

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Using glucocorticoids without insulin resistance

Inflammation can be reduced with chronic glucocorticoid treatment, which unfortunately is associated with the development of insulin resistance. Glucocorticoids induce the production of the secreted protein Angptl4 and of ceramides, a family of lipid mediators. Chen et al. showed that Angptl4 was necessary to induce the expression of genes encoding factors involved in ceramide synthesis in the livers of glucocorticoid-treated mice. Furthermore, Angptl4 was required to stimulate the activity of two downstream effectors of ceramides: PP2A and PKCζ. These results suggest that inhibiting this pathway may alleviate the insulin resistance that occurs with chronic glucocorticoid treatment.