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Adrenergic signaling in insulin-sensitive tissues
Stockholm University, Faculty of Science, Wenner-Gren Institute for Experimental Biology.
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Glucose metabolism in insulin-sensitive tissues such as skeletal muscle and adipose tissue is tightly regulated by external stimuli. Metabolic changes in these tissues have direct effects on whole body metabolism. Such metabolic changes can be induced or influenced by adrenergic stimulation.

In L6 skeletal muscle cells, we have seen that the β2-adrenergic receptor increases glycogen synthesis to the same extent as insulin. The β2-adrenergically mediated effect is independent of cyclic AMP but dependent on PI3K.

In brown adipocytes, our data suggest that signaling from the β-adrenergic receptors consists of an acute cyclic AMP effect that is rapidly desensitized and then a prolonged signal involving PI3K.

In skeletal muscle cells in culture, we have shown that DPI (a NADPH oxidase inhibitor) increases glucose uptake through a signaling pathway independent of NADPH oxidase and insulin signaling. DPI instead inhibits complex 1 in the mitochondrial respiratory chain, which lowers ATP levels. This activates AMPK, an activator of glucose uptake.

Furthermore, we have developed a model system for ordered fusion of skeletal muscle cells in culture. In this system, differentiating skeletal muscle cells can be studied separately. This system is optimal for microscopy techniques and easily adaptable for micromanipulations. We have seen that the myogenic factor MyoD can have different expression of the protein in different nuclei within the same myotube. This system could be used with advantage for intracellular signaling and metabolic studies.

Place, publisher, year, edition, pages
Stockholm: Wenner-Grens institut för experimentell biologi , 2007. , 180 p.
Keyword [en]
Metabolism, Adrenergic, Glucose, Signaling, Skeletal muscle
National Category
Zoology
Research subject
Zoological physiology
Identifiers
URN: urn:nbn:se:su:diva-6668ISBN: 91-7155-395-9 (print)OAI: oai:DiVA.org:su-6668DiVA: diva2:196840
Public defence
2007-03-23, sal E306, Arrheniuslaboratorierna, Svante Arrhenius väg 14-18, Stockholm, 13:00
Opponent
Supervisors
Available from: 2007-03-01 Created: 2007-02-22Bibliographically approved
List of papers
1. β2-adrenergic activation increases glycogen synthesis in L6 skeletal muscle cells through a signalling pathway independent of cyclic AMP
Open this publication in new window or tab >>β2-adrenergic activation increases glycogen synthesis in L6 skeletal muscle cells through a signalling pathway independent of cyclic AMP
2007 In: Diabetologia, ISSN 0012-186X, Vol. 50, no 1, 158-167 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:su:diva-24131 (URN)000243188000022 ()
Note
Part of urn:nbn:se:su:diva-6668Available from: 2007-03-01 Created: 2007-02-22Bibliographically approved
2. β-adrenergic receptor cAMP and PI3K signaling in primary cultures of brown adipocytes.
Open this publication in new window or tab >>β-adrenergic receptor cAMP and PI3K signaling in primary cultures of brown adipocytes.
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Manuscript (Other academic)
Identifiers
urn:nbn:se:su:diva-24132 (URN)
Note
Part of urn:nbn:se:su:diva-6668Available from: 2007-03-01 Created: 2007-02-22 Last updated: 2010-01-13Bibliographically approved
3. Diphenylene iodonium stimulates glucose uptake in skeletal muscle cells through mitochondrial complex I inhibition and activation of AMP-activated protein kinase
Open this publication in new window or tab >>Diphenylene iodonium stimulates glucose uptake in skeletal muscle cells through mitochondrial complex I inhibition and activation of AMP-activated protein kinase
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2007 (English)In: Cellular Signalling, ISSN 0898-6568, E-ISSN 1873-3913, Vol. 19, no 7, 1610-1620 p.Article in journal (Refereed) Published
Abstract [en]

NADPH oxidase inhibitors such as diphenylene iodonium (DPI) and apocynin lower whole body and blood glucose levels and improve diabetes when administered to rodents. Skeletal muscle has an important role in managing glucose homeostasis and we have used L6 cells, C2C12 cells and primary muscle cells as model systems to investigate whether these drugs regulate glucose uptake in skeletal muscle cells. The data presented in this study show that apocynin does not affect glucose uptake in skeletal muscle cells in culture. Tat gp91ds, a chimeric peptide that inhibits NADPH oxidase activity, also failed to affect glucose uptake and we found no significant evidence of NADPH oxidase (subunits tested were Nox4, p22phox, gp91phox and p47phox mRNA) in skeletal muscle cells in culture. However, DPI increases basal and insulin-stimulated glucose uptake in L6 cells, C2C12 cells and primary muscle cells. Detailed studies on L6 cells demonstrate that the increase of glucose uptake is via a mechanism independent of phosphoinositide-3 kinase (PI3K)/Akt but dependent on AMP-activated protein kinase (AMPK). We postulate that DPI through inhibition of mitochondrial complex 1 and decreases in oxygen consumption, leading to decreases of ATP and activation of AMPK, stimulates glucose uptake in skeletal muscle cells.

Keyword
NADPH oxidase, DPI, L6, Glucose uptake, Skeletal muscle, AMPK, Mitochondria
National Category
Biological Sciences
Identifiers
urn:nbn:se:su:diva-24133 (URN)10.1016/j.cellsig.2007.02.006 (DOI)
Available from: 2007-03-01 Created: 2007-02-22 Last updated: 2011-02-17Bibliographically approved
4. Myotube Formation on UV-lithographically Micro-patterned Glass: A New Experimental System for Studies of Muscle differentiation in vitro
Open this publication in new window or tab >>Myotube Formation on UV-lithographically Micro-patterned Glass: A New Experimental System for Studies of Muscle differentiation in vitro
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Article in journal (Refereed) Submitted
Identifiers
urn:nbn:se:su:diva-24134 (URN)
Note
Part of urn:nbn:se:su:diva-6668Available from: 2007-03-01 Created: 2007-02-22Bibliographically approved

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