Insulin signalling and GLUT4 trafficking in insulin resistance.


Type
Article
Change log
Authors
van Gerwen, Julian 
Shun-Shion, Amber S 
Fazakerley, Daniel J  ORCID logo  https://orcid.org/0000-0001-8241-2903
Abstract

Insulin-stimulated glucose uptake into muscle and adipose tissue is vital for maintaining whole-body glucose homeostasis. Insulin promotes glucose uptake into these tissues by triggering a protein phosphorylation signalling cascade, which converges on multiple trafficking processes to deliver the glucose transporter GLUT4 to the cell surface. Impaired insulin-stimulated GLUT4 translocation in these tissues underlies insulin resistance, which is a major risk factor for type 2 diabetes and other metabolic diseases. Despite this, the precise changes in insulin signalling and GLUT4 trafficking underpinning insulin resistance remain unclear. In this review, we highlight insights from recent unbiased phosphoproteomics studies, which have enabled a comprehensive examination of insulin signalling and have transformed our perspective on how signalling changes may contribute to insulin resistance. We also discuss how GLUT4 trafficking is disrupted in insulin resistance, and underline sites where signalling changes could lead to these trafficking defects. Lastly, we address several major challenges currently faced by researchers in the field. As signalling and trafficking alterations can be examined at increasingly high resolution, integrative approaches examining the two in combination will provide immense opportunities for elucidating how they conspire to cause insulin resistance.

Description
Keywords
GLUT4, glucose transport, insulin resistance, insulin signalling, phosphoproteomics, trafficking
Journal Title
Biochem Soc Trans
Conference Name
Journal ISSN
0300-5127
1470-8752
Volume Title
Publisher
Portland Press
Sponsorship
Medical Research Council (MR/S007091/1)

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2023-06-27 13:10:21
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2023-05-19 00:30:53
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