Anti-inflammatory action of insulin targets the innate immunity via protease-activated receptor 2 (PAR-2)

Anti-inflammatory effects of insulin may share a signaling pathway with the protease-activated receptor 2 (PAR-2), a G protein-coupled receptor.

Insulin reduced PAR(2)-induced inflammation in a murine model, attenuated PAR(2)-induced leukocyte trafficking, and reduced PAR(2) calcium signaling.

This effect of insulin to attenuate PAR(2)-mediated inflammation was reversed when cells were preincubated with a pan-protein kinase C inhibitor).

The enhanced inflammatory effect of PAR(2) was attenuated by the local administration of insulin at the inflammatory site.

Anti-inflammatory action of insulin targets the acute innate inflammatory response triggered by PAR(2).

Effect of insulin on glucose uptake and metabolism. Insulin binds to its receptor (1) which in turn starts many protein activation cascades (2). These include: translocation of Glut-4 transporter to the plasma membrane and influx of glucose (3), glycogen synthesis (4), glycolysis (5) and fatty acid synthesis (6). Image source: Wikipedia, public domain.

Insulin Modulates Protease-Activated Receptor 2 Signaling: Implications for the Innate Immune Response. Hyun E, Ramachandran R, Cenac N, Houle S, Rousset P, Saxena A, Liblau RS, Hollenberg MD, Vergnolle N. J Immunol. 2010 Jan 29. [Epub ahead of print]

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