| The Shc locus regulates insulin signaling and adiposity in mammals. | |
| | |
MedLine Citation:
|
PMID: 21040401 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
|
Longevity of a p66Shc knockout strain (ShcP) was previously attributed to increased stress resistance and altered mitochondria. Microarrays of ShcP tissues indicated alterations in insulin signaling. Consistent with this observation, ShcP mice were more insulin sensitive and glucose tolerant at organismal and tissue levels, as was a novel p66Shc knockout (ShcL). Increasing and decreasing Shc expression in cell lines decreased and increased insulin sensitivity, respectively - consistent with p66Shc's function as a repressor of insulin signaling. However, differences between the two p66Shc knockout strains were also observed. ShcL mice were fatter and susceptible to fatty diets, and their fat was more insulin sensitive than controls. On the other hand, ShcP mice were leaner and resisted fatty diets, and their adipose was less insulin sensitive than controls. ShcL and ShcP strains are both highly inbred on the C57Bl/6 background, so we investigated gene expression at the Shc locus, which encodes three isoforms, p66, p52, and p46. Isoform p66 is absent in both strains; thus, the remaining difference to which to attribute the 'lean' phenotype is expression of the other two isoforms. ShcL mice have a precise deletion of p66Shc and normal expression of p52 and p46Shc isoforms in all tissues; thus, a simple deletion of p66Shc results in a 'fat' phenotype. However, ShcP mice in addition to p66Shc deletion have a fourfold increase in p46Shc expression in white fat. Thus, p46Shc overexpression in fat, rather than p66Shc deletion, is the likely cause of decreased adiposity and reduced insulin sensitivity in the fat of ShcP mice, which has implications for the longevity of the strain. |
| | |
Authors:
|
Alexey A Tomilov; Jon J Ramsey; Kevork Hagopian; Marco Giorgio; Kyoungmi M Kim; Adam Lam; Enrica Migliaccio; Kent C Lloyd; Ina Berniakovich; Tomas A Prolla; Piergiuseppe Pelicci; Gino A Cortopassi |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-11-15 |
Journal Detail:
|
Title: Aging cell Volume: 10 ISSN: 1474-9726 ISO Abbreviation: Aging Cell Publication Date: 2011 Feb |
Date Detail:
|
Created Date: 2011-01-12 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 101130839 Medline TA: Aging Cell Country: England |
Other Details:
|
Languages: eng Pagination: 55-65 Citation Subset: IM |
Affiliation:
|
VM-Molecular Biosciences, University of California, Davis, CA 95616 USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
| Grant Support | |
ID/Acronym/Agency:
|
AG025532/AG/NIA NIH HHS; AG16719/AG/NIA NIH HHS; EY12245/EY/NEI NIH HHS |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Pyruvate imbalance mediates metabolic reprogramming and mimics lifespan extension by dietary restric...
Next Document: At the crossroads of longevity and metabolism: the metabolic syndrome and lifespan determinant pathw...