PT  - JOURNAL ARTICLE
AU  - Abhiram Charan Tej Mallu
AU  - Sivapriya Sivagurunathan
AU  - Debasish Paul
AU  - Hobby Aggarwal
AU  - Abel Arul Nathan
AU  - Mahalakshmi M. Ravi
AU  - Ramanamurthy Boppana
AU  - Kumaravelu Jagavelu
AU  - Manas Kumar Santra
AU  - Madhulika Dixit
TI  - Oral glucose feeding enhances adherence of quiescent lymphocytes to fibronectin via non-canonical insulin signalling
AID  - 10.1101/2021.10.13.464163
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.10.13.464163
4099  - http://biorxiv.org/content/early/2021/10/13/2021.10.13.464163.short
4100  - http://biorxiv.org/content/early/2021/10/13/2021.10.13.464163.full
AB  - 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 (PLCγ-1) mediated activation of integrin β1. 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.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-γ1 through Tyr783 phosphorylation, which in turn leads to the activation of integrin β1 through intracellular calcium to ultimately enhance adhesion of quiescent lymphocytes to fibronectin.Competing Interest StatementThe authors have declared no competing interest.