Linked Life Data

20702796

Source:http://linkedlifedata.com/resource/pubmed/id/20702796

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2010-10-1
pubmed:abstractText
Despite numerous clinical studies supporting a link between type 2 diabetes (T2D) and Parkinson's disease (PD), the clinical literature remains equivocal. We, therefore, sought to address the relationship between insulin resistance and nigrostriatal dopamine (DA) in a preclinical animal model. High-fat feeding in rodents is an established model of insulin resistance, characterized by increased adiposity, systemic oxidative stress, and hyperglycemia. We subjected rats to a normal chow or high-fat diet for 5 wk before infusing 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle. Our goal was to determine whether a high-fat diet and the resulting peripheral insulin resistance would exacerbate 6-OHDA-induced nigrostriatal DA depletion. Prior to 6-OHDA infusion, animals on the high-fat diet exhibited greater body weight, increased adiposity, and impaired glucose tolerance. Two weeks after 6-OHDA, locomotor activity was tested, and brain and muscle tissue was harvested. Locomotor activity did not differ between the groups nor did cholesterol levels or measures of muscle atrophy. High-fat-fed animals exhibited higher homeostatic model assessment of insulin resistance (HOMA-IR) values and attenuated insulin-stimulated glucose uptake in fast-twitch muscle, indicating decreased insulin sensitivity. Animals in the high-fat group also exhibited greater DA depletion in the substantia nigra and the striatum, which correlated with HOMA-IR and adiposity. Decreased phosphorylation of HSP27 and degradation of I?B? in the substantia nigra indicate increased tissue oxidative stress. These findings support the hypothesis that a diet high in fat and the resulting insulin resistance may lower the threshold for developing PD, at least following DA-specific toxin exposure.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1522-1490
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
299
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
R1082-90
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:20702796-Animals, pubmed-meshheading:20702796-Blood Glucose, pubmed-meshheading:20702796-Body Weight, pubmed-meshheading:20702796-Cholesterol, pubmed-meshheading:20702796-Chromatography, High Pressure Liquid, pubmed-meshheading:20702796-Dietary Fats, pubmed-meshheading:20702796-Dopamine, pubmed-meshheading:20702796-Eating, pubmed-meshheading:20702796-Epididymis, pubmed-meshheading:20702796-Glucose Tolerance Test, pubmed-meshheading:20702796-Hydrogen Peroxide, pubmed-meshheading:20702796-Insulin, pubmed-meshheading:20702796-Insulin Resistance, pubmed-meshheading:20702796-Iron, pubmed-meshheading:20702796-Male, pubmed-meshheading:20702796-Mice, pubmed-meshheading:20702796-Muscle, Skeletal, pubmed-meshheading:20702796-Neostriatum, pubmed-meshheading:20702796-Nerve Degeneration, pubmed-meshheading:20702796-Neurons, pubmed-meshheading:20702796-Oxidopamine, pubmed-meshheading:20702796-Parkinson Disease, Secondary, pubmed-meshheading:20702796-Rats, pubmed-meshheading:20702796-Rats, Inbred F344, pubmed-meshheading:20702796-Substantia Nigra, pubmed-meshheading:20702796-Sympatholytics
pubmed:year
2010
pubmed:articleTitle
Neurodegeneration in an animal model of Parkinson's disease is exacerbated by a high-fat diet.
pubmed:affiliation
Department of Molecular and Integrative Physiology, Univ. of Kansas Medical Center, Kansas City, 66160, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural