Document Detail

Age-related changes in insulin receptor mRNA and protein expression in genetically obese Zucker rats.
MedLine Citation:
PMID:  20149705     Owner:  NLM     Status:  MEDLINE    
AIM: The mechanisms underlying the age-related decrease in insulin-receptor (IR) binding in genetically obese Zucker rats are not well understood. For this reason, the present study analyzed the expression of IR mRNA and protein in selected tissues from 1- to 4-month-old obese (fa/fa) Zucker rats and lean (Fa/-) age-matched controls. METHODS: The following parameters were evaluated: (1) IR mRNA level, and proportion of isotypes A (exon 11-) and B (exon 11+) of IR mRNA in liver, brain and kidney; (2) level, molecular size and tyrosine phosphorylation of IR-beta subunit in liver subcellular fractions; and (3) stability of liver IR based on sensitivity in vivo of insulin-binding activity and IR-beta levels in response to tunicamycin, a glycosylation inhibitor. RESULTS: At one month, IR mRNA level was increased in liver and brain, but decreased in kidneys and, at four months, both mRNA level and isotype B proportion were decreased in liver. From age two months, the following changes in liver IR protein expression were observed: (1) decreased IR-beta level in whole homogenates, but increased IR-beta levels in endosomal fractions; (2) increased IR-beta tyrosine phosphorylation; and (3) at four months, increased levels of both intact IR-beta (95 kDa) and IR-beta fragments (72 and 52 kDa) in lysosomal fractions, along with decreased stability in vivo of the IR. CONCLUSION: These data show that obese Zucker rats display age-related alterations of IR gene expression at both pre- and post-translational stages and, in particular, increased endocytosis and degradation of IR protein.
M Amessou; K Tahiri; G Chauvet; B Desbuquois
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-02-10
Journal Detail:
Title:  Diabetes & metabolism     Volume:  36     ISSN:  1878-1780     ISO Abbreviation:  Diabetes Metab.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-04-26     Completed Date:  2010-08-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9607599     Medline TA:  Diabetes Metab     Country:  France    
Other Details:
Languages:  eng     Pagination:  120-8     Citation Subset:  IM    
Copyright Information:
(c) 2010 Elsevier Masson SAS. All rights reserved.
Inserm, U674, Paris, France.
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MeSH Terms
Age Factors
Aging / genetics,  metabolism*
Analysis of Variance
Blotting, Western
Gene Expression / drug effects
Gene Expression Profiling / methods
Obesity / genetics,  metabolism*
Organ Specificity
Protein Isoforms / genetics,  metabolism
Protein Stability
RNA, Messenger / genetics,  metabolism*
Rats, Transgenic
Rats, Zucker
Receptor, Insulin / biosynthesis*,  genetics
Receptors, Leptin / genetics
Tunicamycin / pharmacology
Reg. No./Substance:
0/Protein Isoforms; 0/RNA, Messenger; 0/Receptors, Leptin; 11089-65-9/Tunicamycin; EC, Insulin

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