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An insulin-independent pathway including β-adrenoceptors and mTORC2 that translocates GLUT4 and increases glucose uptake in skeletal muscle
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
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(English)Manuscript (preprint) (Other academic)
National Category
Natural Sciences
Identifiers
URN: urn:nbn:se:su:diva-87232OAI: oai:DiVA.org:su-87232DiVA: diva2:601665
Available from: 2013-01-30 Created: 2013-01-30 Last updated: 2013-01-30
In thesis
1. β-adrenergic signalling and novel effects in skeletal muscle
Open this publication in new window or tab >>β-adrenergic signalling and novel effects in skeletal muscle
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Skeletal muscles have, due to their large mass, a big impact on the whole body metabolism. There are many signals that can regulate the functions of skeletal muscles and one such signal is activation of α- and β-adrenoceptors (α- and β-ARs) by epinephrine and norepinephrine. This activation leads to several effects which are examined in this thesis.

 

Stimulation of β-AR on muscle cells induces glucose uptake, an event that both provides the muscle with energy and lowers the blood glucose levels. We discovered two key components in the β-ARs signal to glucose uptake: the transporter protein GLUT4 and the kinase mTOR, a molecule involved in several metabolic processes but not previously known to be activated by β-ARs.

 

The classical second messenger downstream of β-ARs, cAMP, was surprisingly found to be only partly involved in the β-adrenergic glucose uptake. We also found that a molecule called GRK2 is very important for this glucose uptake.

 

A novel effect of β-AR stimulation presented in this thesis is the inhibition of myosin II-dependent contractility in skeletal muscle cells. The intracellular pathway regulating this event was different from that regulating glucose uptake and involved both classical and novel molecules in the β-AR pathway.

 

Another stimulus that we found to activate insulin-independent glucose uptake in skeletal muscle cells was the natural compound Shikonin. Shikonin increased glucose uptake in skeletal muscle cells via a calcium- and GLUT4-dependent mechanism and improved glucose homeostasis in diabetic rats.

 

Taken together, we have identified new key molecules in the adrenergic signaling pathway as well as novel downstream effects. We conclude that glucose uptake in muscles can be activated by β-adrenergic stimulation or by Shikonin and that both treatments improves glucose homeostasis in diabetic animals. This knowledge can hopefully be used in the search for new drugs to combat type II diabetes.

Place, publisher, year, edition, pages
Stockholm: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 2013. 61 p.
National Category
Physiology
Research subject
Physiology
Identifiers
urn:nbn:se:su:diva-87205 (URN)978-91-7447-624-8 (ISBN)
Public defence
2013-03-08, hörsalen, Frescati backe, Svante Arrhenius väg 21 A, Stokcholm, 10:00 (English)
Opponent
Supervisors
Note

At the time of doctoral defence the following papers were unpublished and had a status as follows. Paper 1: Manuscript; Paper 3: Manuscript

Available from: 2013-02-14 Created: 2013-01-29 Last updated: 2013-02-05Bibliographically approved

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Dehvari, NodiÖberg, Anette I.Csikasz, Robert I.Bengtsson, Tore
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