By: Jessica Olsen
Date: 14 June 2017, 14.00 PM – 14 June 2017, 16.00 PM
Venue: E306, Arrheniuslaboratorierna, Svante Arrhenius väg 20 C
Title: β-Adrenergic Signalling Through mTOR

Examination board

Martin Klingenspor, Technical University Munich, Germany (opponent)
Gunnar Schulte, Dept. of Physiology and Pharmocology, Karolinska institute
Anki Östlund Farrant, Dept. of Molecular Biosciences, Wenner-Gren institute, Stockholm University
Eva Blomstrand, The Swedish School of Sport and Health Sciences, GIH
Ulrich Theopold, Dept. of Molecular Biosciences, Wenner-Gren institute, Stockholm University (Chairman of dissertation)


Adrenergic signalling is part of the sympathetic nervous system and is activated upon stimulation by the catecholamines epinephrine and norepinephrine. This regulates heart rate, energy mobilization, digestion and helps to divert blood flowto important organs. Insulin is released to regulate metabolism of carbohydrates, fats and proteins, mainly by taking up glucose from the blood. The insulin and the catecholamine hormone systems are normally working as opposing metabolic regulators and are therefore thought to antagonize each other.

One of the major regulators involved in insulin signalling is the mechanistic target of rapamycin (mTOR). There are two different complexes of mTOR; mTORC1 and mTORC2, and they are essential in the control of cell growth, metabolism and energy homeostasis. Since mTOR is one of the major signalling nodes for anabolic actions of insulin it was thought that catecholamines might oppose this action by inhibiting the complexes. However, lately there are studies demonstrating that this may not be the case. mTOR is for instance part of the adrenergic signalling pathway resulting in hypertrophy of cardiac and skeletal muscle cells and inhibition of smooth muscle relaxation and helps to regulate browning in white adipose tissue and thermogenesis in brown adipose tissue (BAT).

In this thesis I show that β-adrenergic signalling leading to glucose uptake occurs independently of insulin in skeletal muscle and BAT, and does not activate either Akt or mTORC1, but that the master regulator of this pathway is mTORC2. Further, my co-workers and I demonstrates that β-adrenergic stimulation in skeletal muscle and BAT utilizes different glucose transporters. In skeletal muscle, GLUT4 is translocated to the plasma membrane upon stimulation. However, in BAT, β-adrenergic stimulation results in glucose uptake through translocation of GLUT1. Importantly, in both skeletal muscle and BAT, the role of mTORC2 in β-adrenergic stimulated glucose uptake is to regulate GLUT-translocation.

Keywords: Glucose uptake, Brown adipose tissue, White adipose tissue, Skeletal muscle, Mechanistic target of rapamycin, Glucose transporter, Physiology.