Insulin modulates protease-activated receptor 2 signaling: implications for the innate immune response

The Journal of Immunology : Official Journal of the American Association of Immunologists
Eric HyunNathalie Vergnolle

Abstract

Given the anti-inflammatory effects of insulin in human and animal studies done in vivo and given the signaling pathways in common between insulin and the protease-activated receptor 2 (PAR(2)), a G protein-coupled receptor, we hypothesized that insulin would have an impact on the inflammatory actions of PAR(2). We found that low doses or concentrations of insulin in the subnanomolar range reduced PAR(2)-induced inflammation in a murine paw edema model, attenuated PAR(2)-induced leukocyte trafficking in mouse intestinal venules, and reduced PAR(2) calcium signaling in cultured dorsal root ganglion neurons and endothelial cells. This effect of insulin to attenuate PAR(2)-mediated inflammation was reversed when cells were preincubated with LY294002 (a PI3K inhibitor) and GF 109203X (a pan-protein kinase C inhibitor). The enhanced inflammatory effect of PAR(2) observed in vivo in an insulin-deficient murine type 1 diabetes model was attenuated by the local administration of insulin at the inflammatory site. Our data point to an anti-inflammatory action of insulin that targets the acute innate inflammatory response triggered by PAR(2).

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Citations

Aug 18, 2012·Evidence-based Complementary and Alternative Medicine : ECAM·Mohamed EddouksNaoufel Ali Zeggwagh
Feb 28, 2015·Biological Research·Gustavo OrtizJuan E Gallo
Sep 30, 2016·Pharmacological Reviews·Rithwik RamachandranMorley D Hollenberg
Sep 29, 2011·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Jaime HaidetPatrizia Luppi
Jun 16, 2014·American Journal of Physiology. Heart and Circulatory Physiology·Lusha XiangRobert L Hester
Jan 18, 2017·Gut·Claire Rolland-FourcadeNathalie Vergnolle
Nov 10, 2011·The American Journal of Pathology·Thomas GobbettiNathalie Vergnolle

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