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    A High-Fat Diet Alters the Phenotype of Diabetic Neuropathy

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    Guilford_ku_0099D_12825_DATA_1.pdf (5.637Mb)
    Issue Date
    2013-05-31
    Author
    Guilford, Brianne Lynn
    Publisher
    University of Kansas
    Format
    201 pages
    Type
    Dissertation
    Degree Level
    Ph.D.
    Discipline
    Anatomy & Cell Biology
    Rights
    This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
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    Abstract
    Diabetic neuropathy is a principal chronic complication of both type 1 and type 2 diabetes and affects over half of diabetic patients. This debilitating disease presents with a dichotomous phenotype such that affected patients can experience both negative and positive sensory symptoms including chronic numbness, altered sensitivity to pain or touch, and impaired proprioception. In light of long withstanding evidence that hyperglycemia is the primary cause of diabetic neuropathy, evidence from several large clinical studies indicate metabolic defects such as a poor lipid profile are linked with neuropathy development and progression, independent of glycemic control. Consequently, dyslipidemia has recently been identified as an independent risk factor for diabetic neuropathy. The purpose of this body of work was to test the effects of diet and dyslipidemia on the development and progression of diabetic neuropathy and identify potential mechanisms underlying the pathogenesis of high-fat diet induced neuropathy. Initial studies characterized the effects of a high-fat diet on neuropathy progression and phenotype in nondiabetic and streptozocin (STZ) induced (type 1 model) diabetic mice. STZ-induced diabetic C57Bl/6 mice fed a high-fat diet developed dyslipidemia and a painful neuropathy (mechanical hyperalgesia) instead of the insensate neuropathy (mechanical insensitivity) that normally develops in this mouse strain. Nondiabetic mice fed the high-fat diet also developed dyslipidemia and mechanical hyperalgesia. These findings are particularly important because it suggests that diet may modulate diabetic neuropathy phenotype. Second, mitochondrial dysfunction, inflammation, and peripheral nervous system insulin resistance were investigated as potential mechanisms underlying the pathogenesis of high-fat diet induced painful neuropathy. Results from these studies suggest that none of these mechanisms are driving the robust behavioral phenotype observed in high-fat-fed nondiabetic and streptozocin-induced diabetic mice. Finally, exercise ameliorated the detrimental effects of a high-fat diet on body weight, circulating glucose and insulin levels, and skeletal muscle insulin resistance. These results reinforced the importance of exercise in preventing or reversing symptoms of diabetes. Together, these studies provide strong evidence for the influence of lifestyle factors, including diet and physical activity, on metabolic defects and neural complications associated with diabetes.
    URI
    http://hdl.handle.net/1808/12177
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    • KU Med Center Dissertations and Theses [149]
    • Dissertations [4050]

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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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