Linked Life Data

19211686

Source:http://linkedlifedata.com/resource/pubmed/id/19211686

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2009-3-23
pubmed:abstractText
Diabetic nephropathy is the leading cause of end-stage renal disease and the largest contributor to the total cost of diabetes care. Rodent models are excellent tools to gain more insight into the pathogenesis of diabetic nephropathy. In the present study, we characterize the age-related sequence of diabetes-associated kidney lesions in GIPR(dn) transgenic mice, a novel mouse model of early-onset diabetes mellitus. Clinical-chemical analyses as well as qualitative and quantitative morphological analyses of the kidneys of GIPR(dn) transgenic animals and nontransgenic littermate controls were performed at 3, 8, 20, and 28 wk of age. Early renal changes of transgenic mice consisted of podocyte hypertrophy, reduced numerical volume density of podocytes in glomeruli, and homogenous thickening of the glomerular basement membrane, followed by renal and glomerular hypertrophy as well as mesangial expansion and matrix accumulation. At 28 wk of age, glomerular damage was most prominent, including advanced glomerulosclerosis, tubulointerstitial lesions, and proteinuria. Real-time PCR demonstrated increased glomerular expression of Col4a1, Fn1, and Tgfb1. Immunohistochemistry revealed increased mesangial deposition of collagen type IV, fibronectin, and laminin. The present study shows that GIPR(dn) transgenic mice exhibit renal changes that closely resemble diabetes-associated kidney alterations in humans. Data particularly from male transgenic mice indicate that podocyte hypertrophy is directly linked to hyperglycemia, without the influence of mechanical stress. GIPR(dn) transgenic mice are considered an excellent new tool to study the mechanisms involved in onset and progression of diabetic nephropathy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1931-857X
pubmed:author
pubmed:issnType
Print
pubmed:volume
296
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
F819-29
pubmed:dateRevised
2011-4-28
pubmed:meshHeading
pubmed-meshheading:19211686-Age Factors, pubmed-meshheading:19211686-Albuminuria, pubmed-meshheading:19211686-Animals, pubmed-meshheading:19211686-Blood Glucose, pubmed-meshheading:19211686-Blood Pressure, pubmed-meshheading:19211686-Body Weight, pubmed-meshheading:19211686-Caloric Restriction, pubmed-meshheading:19211686-Collagen Type IV, pubmed-meshheading:19211686-Diabetes Mellitus, Type 2, pubmed-meshheading:19211686-Diabetic Nephropathies, pubmed-meshheading:19211686-Disease Models, Animal, pubmed-meshheading:19211686-Disease Progression, pubmed-meshheading:19211686-Female, pubmed-meshheading:19211686-Fibronectins, pubmed-meshheading:19211686-Glomerular Basement Membrane, pubmed-meshheading:19211686-Humans, pubmed-meshheading:19211686-Hypertrophy, pubmed-meshheading:19211686-Laminin, pubmed-meshheading:19211686-Male, pubmed-meshheading:19211686-Mice, pubmed-meshheading:19211686-Mice, Transgenic, pubmed-meshheading:19211686-Mutation, pubmed-meshheading:19211686-Organ Size, pubmed-meshheading:19211686-Podocytes, pubmed-meshheading:19211686-Receptors, Gastrointestinal Hormone, pubmed-meshheading:19211686-Transforming Growth Factor beta1
pubmed:year
2009
pubmed:articleTitle
Diabetic kidney lesions of GIPRdn transgenic mice: podocyte hypertrophy and thickening of the GBM precede glomerular hypertrophy and glomerulosclerosis.
pubmed:affiliation
Institute of Veterinary Pathology, Veterinaerstr. 13, 80539 Munich, Germany. herbach@patho.vetmed.uni-muenchen.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't