RT Journal Article
SR Electronic
T1 Oral glucose feeding enhances adherence of quiescent lymphocytes to fibronectin via non-canonical insulin signalling
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.10.13.464163
DO 10.1101/2021.10.13.464163
A1 Abhiram Charan Tej Mallu
A1 Sivapriya Sivagurunathan
A1 Debasish Paul
A1 Hobby Aggarwal
A1 Abel Arul Nathan
A1 Mahalakshmi M. Ravi
A1 Ramanamurthy Boppana
A1 Kumaravelu Jagavelu
A1 Manas Kumar Santra
A1 Madhulika Dixit
YR 2021
UL http://biorxiv.org/content/early/2021/10/13/2021.10.13.464163.abstract
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.