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

Abhiram Charan Tej Mallu, Sivapriya Sivagurunathan, Debasish Paul, Hobby Aggarwal, Abel Arul Nathan, Mahalakshmi M. Ravi, Ramanamurthy Boppana, Kumaravelu Jagavelu, Manas Kumar Santra, Madhulika Dixit
doi: https://doi.org/10.1101/2021.10.13.464163
Abhiram Charan Tej Mallu
1Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai-600036, India
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Sivapriya Sivagurunathan
1Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai-600036, India
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Debasish Paul
2National Centre for Cell Science, Savitribai Phule Pune University Campus, Pune-411007, India
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Hobby Aggarwal
3Pharmacology Division, CSIR-Central Drug Research Institute, Sitapur Road, Lucknow-226031, India
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Abel Arul Nathan
1Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai-600036, India
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Mahalakshmi M. Ravi
4Institute Hospital, Indian Institute of Technology Madras, Chennai-600036, India
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Ramanamurthy Boppana
2National Centre for Cell Science, Savitribai Phule Pune University Campus, Pune-411007, India
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Kumaravelu Jagavelu
3Pharmacology Division, CSIR-Central Drug Research Institute, Sitapur Road, Lucknow-226031, India
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Manas Kumar Santra
2National Centre for Cell Science, Savitribai Phule Pune University Campus, Pune-411007, India
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Madhulika Dixit
1Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai-600036, India
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  • For correspondence: mdixit@iitm.ac.in
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Summary

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.

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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 Statement

The authors have declared no competing interest.

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Posted October 13, 2021.
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Oral glucose feeding enhances adherence of quiescent lymphocytes to fibronectin via non-canonical insulin signalling
Abhiram Charan Tej Mallu, Sivapriya Sivagurunathan, Debasish Paul, Hobby Aggarwal, Abel Arul Nathan, Mahalakshmi M. Ravi, Ramanamurthy Boppana, Kumaravelu Jagavelu, Manas Kumar Santra, Madhulika Dixit
bioRxiv 2021.10.13.464163; doi: https://doi.org/10.1101/2021.10.13.464163
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Oral glucose feeding enhances adherence of quiescent lymphocytes to fibronectin via non-canonical insulin signalling
Abhiram Charan Tej Mallu, Sivapriya Sivagurunathan, Debasish Paul, Hobby Aggarwal, Abel Arul Nathan, Mahalakshmi M. Ravi, Ramanamurthy Boppana, Kumaravelu Jagavelu, Manas Kumar Santra, Madhulika Dixit
bioRxiv 2021.10.13.464163; doi: https://doi.org/10.1101/2021.10.13.464163

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