PhD defence: Revisiting GLUT4 whereabouts in adult skeletal muscle

illustration

Kaspar Wredstrøm Persson

PhD thesis

Type 2 diabetes is a major global health concern, with skeletal muscle insulin resistance being an early and important hallmark. In healthy muscle, insulin stimulates GLUT4 translocation to the sarcolemma and T-tubules to enable glucose uptake - a process impaired in insulin resistance. Yet, the trafficking defects underlying this impairment remain poorly defined, particularly in adult skeletal muscle.

This PhD project established and applied advanced imaging workflows - including exofacial GLUT4 antibody detection, proximity ligation assay, and correlative light and electron microscopy - to assess endogenous GLUT4 translocation and localization with subcellular precision in rodent and human skeletal muscle.

Our findings demonstrate that GLUT4 translocation to the sarcolemma and T-tubules can be directly detected in adult muscle, and that insulin resistance is associated with GLUT4 mislocalization and reduced storage vesicle content. These advances enable new mechanistic insights into GLUT4 dynamics in health and disease.

Download Table of content; Abstract; Resumé; Encloaed manuscripts; Publications not included in the thesis.

2025, 159 pages.

Time

14 August 2025, 13:00

Place

Aud. 1, August Krogh Building, Universitetsparken 13, DK-2100 Copenhagen.

Opponents

Associate professor Anne Yael Nossen (chair), Department of Nutrition, Exercise and Sports, University of Copenhagen, Denmark.

Associate professor Joachim Nielsen, University of Southern Denmark, Denmark.

Associate professor Daniel Fazakerley, Cambridge University, UK.

Supervisor

Professor Thomas E. Jensen, Department of Nutrition, Exercise and Sports, University of Copenhagen, Denmark.