Mitochondria, lipotoxicity and skeletal muscle metabolism: Implications...


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Title Mitochondria, lipotoxicity and skeletal muscle metabolism: Implications for type 2 diabetes mellitus
Period 12 / 2008 - 10 / 2014
Status Completed
Dissertation Yes
Research number OND1332952
Data Supplier NWO


The aim of this project is to examine the putative role of lipotoxicity in the development of mitochondrial dysfunction, and to investigate the role of mild mitochondrial uncoupling in the protection of mitochondria against lipotoxic effects. We hypothesize that mitochondrial uncoupling, the process of proton gradient lowering, is a powerful protective mechanism to preserve mitochondrial functional capacity via reduction of ROS production. By improving the mitochondrial function the insulin sensitivity should be increased as well. The focus of the project is on skeletal muscle. Research In this project (transgenic) animal experiments will be performed, and state of the art technologies will be used to study the effects of mild mitochondrial uncoupling on mitochondrial function and insulin sensitivity both in vivo and ex vivo. Also the amount of lipid peroxidation and mitochondrial ROS-production will be determined. This project will provide new information on the involvement of muscular lipotoxicity in mitochondrial dysfunction in type 2 diabetes, and increase our understanding on the role of uncoupling in skeletal muscle.

Abstract (NL)

Suikerziekte (diabetes) ontstaat doordat vet stapelt in onze spieren. Te veel vet in de spier kan leiden tot beschadiging van de mitochondria energiecentrales van de cel. De onderzoekers gaan bestuderen of deze beschadiging de oorzaak is van het ontstaan van diabetes.

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Supervisor Prof.dr. M.K.C. Hesselink
Supervisor Prof.dr. P.A.J. Schrauwen
Co-supervisor Dr. J. Hoeks
Doctoral/PhD student Dr. B.W.J. van Bree

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