PhD defence: Acute effects of beta2-adrenoceptor agonist in humans

Glucometabolic regulation in muscle and therapeutic perspectives

Johan Onslev

PhD thesis

With the ongoing increase in global prevalence of metabolic syndrome and type II diabetes, development of new therapeutics to combat these are needed. One suggested approach is to target the beta2-adrenoceptor with beta2-adrenoceptor agonist due to the beneficial effects on whole-body insulin sensitivity after long-term treatment in humans.

However, less is known about the impact of acute beta2-adrenoceptor agonist on glucometabolic regulation in muscle and how this may influence the therapeutic potential of beta2-adrenoceptor agonists in type II diabetes.

Utilizing the invasive methodologies arteriovenous catheterization and muscle biopsy collection throughout three studies combined with state-of-the-art muscle analyses such as muscle metabolomics, this thesis seeks to delineate the acute effect of beta2-agonist on muscle glucometabolic regulation in humans at rest, during exercise, in recovery from exercise and during insulin stimulation.

The broad characterization of the impact of acute beta2 -adrenoceptor agonist during different conditions allows this thesis to broaden the knowledge about the glucometabolic regulation by beta2-adrenoceptor agonist in muscle in humans and to assess how
this may influence the therapeutic potential of beta2-adrenoceptor agonist in humans going forward.

Download Table of contents; List of studies; Summary; Dansk resumé.

2023, 142 pages.

Time

3 April 2023, 13:00

Place

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

Opponents

Professor Ylva Hellsten (chair), Department of Nutrition, Exercise and Sports, University of Copenhagen, Denmark.

Professor John P. Kirwan, Pennington Biomedical Research Center, Louisiana State University, Louisiana, USA.

Associate Professor Esben Søndergaard, Department of Clinical Medicine and Steno Diabetes Center Aarhus, Aarhus University, Aarhus.

Supervisor

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

Co-supervisor

Associate Professor Morten Hostrup, Department of Nutrition, Exercise and Sports, University of Copenhagen, Denmark.

The thesis is available for inspection at Nørre Allé 51, DK-2200 Copenhagen N.