Imperial College London
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DrJorgeBernardino de la Serna

Faculty of Medicine, National Heart & Lung Institute

Senior Lecturer in Inhalation Toxicology and Pharmacology
 
 
 
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Contact

 

+44 (0)20 7594 3277j.bernardino-de-la-serna Website

 
 
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Location

 

CubicleSir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Manchanda:2022:10.1101/2022.08.17.504231,
author = {Manchanda, Y and Bitsi, S and Chen, S and Broichhagen, J and de, la Serna JB and Jones, B and Tomas, A},
doi = {10.1101/2022.08.17.504231},
title = {An examination of the divergent spatiotemporal signaling of GLP-1R <i>versus</i> GIPR in pancreatic beta cells},
url = {http://dx.doi.org/10.1101/2022.08.17.504231},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - <jats:title>Abstract</jats:title><jats:p>The incretin receptors, glucagon-like peptide-1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR), are class B GPCRs and prime therapeutic targets for the treatment of type 2 diabetes (T2D) and obesity. They are expressed in pancreatic beta cells where they potentiate insulin release in response to food intake. Despite GIP being the main incretin in healthy individuals, GLP-1R has been favoured <jats:italic>versus</jats:italic> GIPR as a therapeutic target due to GIPR responses being blunted in T2D patients and the conflicting effects of GIPR agonists and antagonists in improving glucose tolerance and preventing weight gain. There is, however, a recently renewed interest in GIPR biology following the realisation that GIPR responses can be restored after an initial period of blood glucose normalization and the recent development of dual GLP-1R-GIPR agonists with superior capacity for the control of blood glucose levels and weight. The importance of GLP-1R trafficking and subcellular signaling in the control of receptor outputs is well established, but little is known about the pattern of spatiotemporal signaling from the GIPR in beta cells. Here we have directly compared the main trafficking and signaling characteristics of both receptors in pancreatic beta cells, finding striking differences in their propensities for internalization, recycling, and degradation, as well as plasma membrane <jats:italic>versus</jats:italic> endosomal activity, with potential implications for receptor-specific control of beta cell function.</jats:p>
AU  - Manchanda,Y
AU  - Bitsi,S
AU  - Chen,S
AU  - Broichhagen,J
AU  - de,la Serna JB
AU  - Jones,B
AU  - Tomas,A
DO  - 10.1101/2022.08.17.504231
PY  - 2022///
TI  - An examination of the divergent spatiotemporal signaling of GLP-1R <i>versus</i> GIPR in pancreatic beta cells
UR  - http://dx.doi.org/10.1101/2022.08.17.504231
ER  -
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