The role and regulation of pyruvate dehydrogenase in skeletal muscle bioenergetics and type 2 diabetes
As of 2015 over 30 million people had type 2 diabetes with another 84.1 million with prediabetes comprising 350303% of the adult US population. The hallmark of this disease is characterized by impaired glycemic control exhibiting elevations in blood glucose in the post-absorptive and absorptive states. Skeletal muscle comprises 400303% of total body mass and is an early site of insulin resistance. Skeletal muscle contributes to whole body glycemic control through mitochondrial glucose oxidation which is catalyzed and regulated by pyruvate dehydrogenase (PDH). Early type 1 diabetic rodent studies implicated reduced muscle PDH activity in the etiology of hyperglycemia but current human studies indicate either normal or elevated post-absorptive glucose oxidation in resting or contracting skeletal muscle. There is a surprising lack of studies and detailed understanding of the regulation of PDH activity in vivo, especially regarding type 2 diabetes. This dissertation will determine the mechanisms that regulate skeletal muscle PDH activation in vivo, the effects of altered PDH activation on muscle function and finally will quantify PDH activity in a rodent model of type 2 diabetes.
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- In Collections
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Electronic Theses & Dissertations
- Copyright Status
- In Copyright
- Material Type
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Theses
- Authors
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Kasper, Jonathan D.
- Thesis Advisors
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Wiseman, Robert W.
- Committee Members
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Meyer, Ronald A.
Olson, Lawrence K.
Mohr, Susanne
Beard, Daniel A.
- Date
- 2018
- Subjects
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Striated muscle--Physiology
Pyruvate carboxylase
Oxidation, Physiological
Type 2 diabetes
Glucose--Physiological transport
- Program of Study
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Physiology - Doctor of Philosophy
- Degree Level
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Doctoral
- Language
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English
- Pages
- xii, 164 pages
- ISBN
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9780438749054
0438749057
- Permalink
- https://doi.org/doi:10.25335/7nqv-bd94