Oral glucose feeding enhances adherence of quiescent lymphocytes to fibronectin via non-canonical insulin signalling.

Mallu, A. C. T.; Sivagurunathan, S.; Paul, D.; Aggarwal, H.; Nathan, A. A.; Ravi, M. M.; Boppana, R.; Jagavelu, K.; Santra, M. K.; Dixit, M.

doi:10.1101/2021.10.13.464163

bioRxiv · 10.1101/2021.10.13.464163

Oral glucose feeding enhances adherence of quiescent lymphocytes to fibronectin via non-canonical insulin signalling.

Mallu, A. C. T.·Sivagurunathan, S.·Paul, D.·Aggarwal, H.·Nathan, A. A.·Ravi, M. M.·Boppana, R.·Jagavelu, K.·Santra, M. K.·Dixit, M.

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Abstract

Impaired glucose metabolism is associated with chronic inflammation, aberrant immunity and anomalous leukocyte trafficking. Conversely, infusion of functional immune cells restores glucose metabolism. Despite being exposed to periodic alterations in blood insulin levels upon fasting and feeding, studies exploring the physiological effects of these hormonal changes on quiescent circulating lymphocytes are missing. Here we find that oral glucose load in healthy men and mice enhance adherence of circulating peripheral blood mononuclear cells (PBMCs) to fibronectin. This led to increased homing of post-load PBMCs to injured blood vessels. Cell culture based experiments on Jurkat-T cells and PBMCs demonstrated that insulin elicits these adhesive effects through a non-canonical signalling involving insulin growth factor-1 receptor (IGF-1R) and phospholipase C gamma-1 (PLC{gamma}-1) mediated activation of integrin {beta}1. Our findings point to the relevance of post-prandial insulin spikes in regulating homing of circulating T-cells to various organs for tissue repair and immunity. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=123 SRC="FIGDIR/small/464163v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@11edce6org.highwire.dtl.DTLVardef@1389835org.highwire.dtl.DTLVardef@90c96eorg.highwire.dtl.DTLVardef@1988a63_HPS_FORMAT_FIGEXP M_FIG Insulin mediates fibronectin adherence of lymphocytes through non-canonical signalling. Insulin mediates auto-phosphorylation of IGF-1 receptor at Tyr1135 leading to activation of PLC-{gamma}1 through Tyr783 phosphorylation, which in turn leads to the activation of integrin 1 through intracellular calcium to ultimately enhance adhesion of quiescent lymphocytes to fibronectin. C_FIG

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Mallu, A. C. T., Sivagurunathan, S., Paul, D., Aggarwal, H., Nathan, A. A., Ravi, M. M., Boppana, R., Jagavelu, K., Santra, M. K., Dixit, M.. 2021-10-13. Oral glucose feeding enhances adherence of quiescent lymphocytes to fibronectin via non-canonical insulin signalling.. https://doi.org/10.1101/2021.10.13.464163

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