PhD defence - Peter Hjorth Albers

Peter Hjorth Albers is defending his PhD thesis

Regulation of metabolic signalling in human skeletal muscle

Impact of gastric bypass, insulin and exercise in a muscle fiber type perspective

Time

20 June 2014 at 14:00

Venue

Auditorium 1, August Krogh building, Universitetsparken 13, Copenhagen

Opponents

Associate professor Nikolai Nordsborg (chair), Department of Nutrition, Exercise and Sports, University of Copenhagen, Denmark

MD PhD Niels Jessen, Department of Clinical Medicine - Molekylær Medicinsk afdeling (MOMA),  Aarhus University Hospital, Denmark

Professor Jørgen Jensen, Department of Physical Performance, Norwegian School of Sport Sciences, Norway

Supervisor

Professor Jørgen Wojtaszewski, Department of Nutrition, Exercise and Sports, University of Copenhagen, Denmark

About the thesis

Muscles are important for energy metabolism. Muscle metabolism is regulated by proteins signaling to other proteins (protein signaling). Muscles consist of different muscle fibers. These fibers possess different properties. For instance, it is expected that energy metabolism is different among different muscle fibers, which is likely reflected on protein signaling.

The present PhD thesis investigated whether different human muscle fibers responded in the same manner to the hormone insulin and physical activity – both stimuli changes the metabolism of muscles. It is concluded, that during insulin stimulated conditions protein signaling in the two investigated muscle fiber types is similar. In contrast, protein signaling is different in different muscle fiber types during physical activity, especially during intermittent exercise.

The dissertation underlines the importance of muscle fiber type specific analysis, since differences in metabolism between different muscle fiber types seem to be dependent on the given stimuli (physical activity versus stimulation by insulin). 

More about the thesis

Regulation of glucose metabolism, despite intense research through decades, is still not clear. Skeletal muscle is highly important for maintaining glucose homeostasis. Regulation of skeletal muscle glucose metabolism is influenced by protein signaling and changes in the activity of metabolic enzymes. Skeletal muscle consists of thousands of muscle fibers.  These fibers can roughly be classified into type I and type II muscle fibers.

The overall aim of this PhD thesis was to investigate the effect of insulin and exercise on human muscle fiber type specific metabolic signaling.

The importance of human type I muscle fibers is illustrated by the finding of a positive correlation between the relative distribution of type I fibers in the muscle and whole-body insulin sensitivity. This suggests, that type I muscle fibers are more insulin sensitive than type II muscle fibers. Improved insulin sensitivity in type I muscle fibers possibly reflects a superior effect of insulin on metabolic signaling compared to type II muscle fibers. This was investigated in the present thesis by examining muscle biopsies from lean and obese healthy subjects as well as patients with type 2 diabetes. From these muscle biopsies, single muscle fibers were dissected. Muscle fiber type determination was performed and fibers were pooled in groups of type I and II muscle fibers. Muscle fiber pools were investigated for regulation of signaling molecules and enzymes, involved in glucose metabolism. Irrespective of the group of subjects investigated, results suggest that the sensitivity to insulin to regulate these signaling proteins is similar in type I and II muscle fibers. On the other hand, abundance of metabolic enzymes is higher in type I compared to type II muscle fibers. This suggests, that type I muscle fibers have a higher glucose handling capacity compared to type II muscle fibers.

To investigate whether regulation of proteins involved in glucose metabolism during an acute bout of exercise is muscle fiber type specific, muscle biopsies from young healthy men were taken. Subjects performed either continuous or interval exercise. Samples of type I and II muscle fibers were prepared as described above. Results indicate that the regulation of the metabolic protein AMP-activated protein kinase (AMPK) and downstream targets is similar in type I and II muscle fibers during continuous exercise. In contrasts, a decreased regulation of these proteins were evident in type I vs II muscle fibers during interval exercise.

The overall conclusion is that metabolic signaling in type I and II muscle fibers in some cases are similar (during insulin stimulation or continuous exercise) and in other cases are different (during interval exercise). The abundance of signaling proteins and metabolic enzymes are in most cases different in type I and type II muscle fibers, indicating that their glucose metabolism is different.

2014, 184 pages ISBN 978 87 7611 762 7