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Caveolar dysfunction leads to signal transduction defects that are critical for obesity-driven disorders

Venugopal, Joshi. Caveolar dysfunction leads to signal transduction defects that are critical for obesity-driven disorders. 2006, Doctoral Thesis, University of Basel, Faculty of Science.

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Official URL: http://edoc.unibas.ch/diss/DissB_7757

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Abstract

To say that obesity and diabetes have reached epidemic proportions has become something of a cliché. This should not lead us to simply accept it as a byproduct of our changing lifestyle, or to overlook the socioeconomic importance of these conditions.
Our attempts at therapeutic intervention have been hindered by a lack of knowledge about the precise pathophysiological mechanisms via which obesity triggers secondary disorders such as diabetes and cardiovascular problems. Our approach to understanding the mechanisms have been largely focused on single molecules whose levels or activity are altered in obesity, and which are known independently to contribute to these secondary disorders. Although we have accumulated genetic and biochemical evidence for the potential role of these factors in these disorders, it must be noted that no single candidate or mechanism has yet given a satisfactory explanation for all the obesity-related disorders. This has led researchers to conclude that the underlying pathology is polygenic or multi-factorial. However, based on our experiments and the recent findings of a few other laboratories, we propose a unifying theory where obesity leads to a membrane microdomain disorder that will in turn lead to the corruption of multiple signaling pathways that are known to be implicated in insulin resistance and cardiovascular disorders. We also explore the possibility of pharmacologically modulating a nodal, but downstream, drug target that might retard or prevent these disorders. Having said that, I would like to clearly state that this theory is still in its infancy, and remains to be tested in both animal models and human subjects.
Advisors:Monard, Denis
Committee Members:Hynes, Nancy and Nagamine, Yoshikuni
Faculties and Departments:09 Associated Institutions > Friedrich Miescher Institut FMI
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:7757
Thesis status:Complete
Bibsysno:Link to catalogue
Number of Pages:130
Language:English
Identification Number:
Last Modified:23 Feb 2018 11:42
Deposited On:13 Feb 2009 15:52

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