Linked Life Data

17762172

Source:http://linkedlifedata.com/resource/pubmed/id/17762172

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2007-8-31
pubmed:abstractText
Glycosuria is one of the well-documented characteristics in ClC-5 knockout (KO) mice and patients with Dent's disease. However, the underlying pathophysiology of its occurrence is unknown. In this study, we have compared ClC-5 KO mice with age and gender matched wild-type (WT) control mice to investigate if the underlying cause of manifested glycosuria is an impairment of glucose homeostasis and/or an alteration in expression levels of proximal tubule (PT) glucose transporters. We observed that, the blood glucose concentration (n=12, p<0.01) and the fractional excretion of glucose and insulin (n=6, p<0.05) were higher in KO mice. In contrast, the fasting blood glucose levels (n=7) were not significantly different in the two groups. Plasma glucose increased to a greater extent in KO mice (n=7, p<0.05) when challenged by an intraperitoneal injection of glucose. However, no peripheral tissue insulin resistance was observed following an intraperitoneal injection of insulin (n=9) in the KO mice. ELISA analysis demonstrated low plasma insulin concentrations after a 12 hour fasting period and also following glucose injection in KO mice. The total insulin released during a 2 hour period following glucose challenge was significantly lower in KO mice (n=6, p<0.05). By western blot, we observed a significant decrease in GLUT2 protein expression levels in isolated PT ((n=10, p<0.01)) of KO mice. This decrease in protein levels was corroborated by a significant decrease in GLUT2 mRNA levels estimated semi quantitatively by RT-PCR in isolated PT (n=10, p<0.01). No significant changes in mRNA expression levels of SGLT2, SGLT1 and GLUT1, as analyzed by RT-PCR, could be detected in the isolated PT (n=10). Also, we have shown by western blot analysis that expression of megalin is lower in the renal cortex of KO mice when compared to WT mice (n=3, p<0.05). Our results suggest that low plasma insulin concentration together with renal function changes observed in KO mice significantly contribute towards the glucose intolerance and documented glycosuria observed in this animal.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1015-8987
pubmed:author
pubmed:copyrightInfo
Copyright (c) 2007 S. Karger AG, Basel.
pubmed:issnType
Print
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
455-64
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Absence of ClC5 in knockout mice leads to glycosuria, impaired renal glucose handling and low proximal tubule GLUT2 protein expression.
pubmed:affiliation
Department of Physiology, The Johns Hopkins University, School of Medicine, Baltimore, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural