AbstractsMedical & Health Science

Glucose transporter 4 (GLUT4) in skeletal muscle plays a vital role in the maintenance of glucose homeostasis. Chapter 2 of this thesis develops an immunofluorescence microscopy method to generate novel information in human skeletal muscle on the effect of physiological stimuli on GLUT4 localisation, translocation to the plasma membrane and total protein content. Chapter 3 shows that training-induced increases in total GLUT4 protein content are driven by increases in the number of large and size of smaller intracellular GLUT4 storage clusters in human skeletal muscle. In chapter 4 the method successfully demonstrates GLUT4 translocation 30 min following glucose ingestion and 30 min after the start of moderate intensity cycling exercise in humans. GLUT4 translocation after glucose ingestion is transient and modest in comparison to the exercise response. Chapters 5 and 6 report no changes in GLUT4 translocation following an 80 min hyperinsulinaemic-isoglycaemic clamp in rats and a 2 h hyperglycaemic clamp in humans despite elevated rates of whole body glucose disposal in both experiments. This immunofluorescence method will be a valuable analytical tool in future studies investigating the mechanisms behind changes in muscle glucose uptake in response to obesity, age-related chronic diseases and therapeutic interventions including diet and exercise.