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IGF-1 protects against diabetic features in an in vivo model of Huntington's disease.

Duarte, Ane; Petit, Géraldine LU ; Ranganathan, Srikanth LU ; Li, Jia-Yi LU ; Oliveira, C R; Brundin, Patrik LU ; Björkqvist, Maria LU and Rego, A C (2011) In Experimental Neurology 231. p.314-319
Abstract
Huntington's disease (HD) is the most prevalent polyglutamine expansion disorder. HD is caused by an expansion of CAG triplet in the huntingtin (HTT) gene, associated with striatal and cortical neuronal loss. Central and peripheral metabolic abnormalities and altered insulin-like growth factor-1 (IGF-1) levels have been described in HD. Thus, we hypothesized that restoration of IGF-1-mediated signaling pathways could rescue R6/2 mice from metabolic stress and behavioral changes induced by polyglutamine expansion. We analyzed the in vivo effect of continuous peripheral IGF-1 administration on diabetic parameters, body weight and motor behavior in the hemizygous R6/2 mouse model of HD. We used 9week-old and age-matched wild-type mice,... (More)
Huntington's disease (HD) is the most prevalent polyglutamine expansion disorder. HD is caused by an expansion of CAG triplet in the huntingtin (HTT) gene, associated with striatal and cortical neuronal loss. Central and peripheral metabolic abnormalities and altered insulin-like growth factor-1 (IGF-1) levels have been described in HD. Thus, we hypothesized that restoration of IGF-1-mediated signaling pathways could rescue R6/2 mice from metabolic stress and behavioral changes induced by polyglutamine expansion. We analyzed the in vivo effect of continuous peripheral IGF-1 administration on diabetic parameters, body weight and motor behavior in the hemizygous R6/2 mouse model of HD. We used 9week-old and age-matched wild-type mice, subjected to continuously infused recombinant IGF-I or vehicle, for 14days. IGF-1 treatment prevented the age-related decrease in body weight in R6/2 mice. Although blood glucose levels were higher in R6/2 mice, they did not reach a diabetic state. Even though, IGF-1 ameliorated poor glycemic control in HD mice. This seemed to be associated with a decrease in blood insulin levels in R6/2 mice, which was increased following IGF-1 infusion. Similarly, blood IGF-1 levels decreased during aging in both wild-type and R6/2 mice, being significantly improved upon its continuous infusion. Although no significant differences were found in motor function in R6/2-treated mice, IGF-1 treatment highly improved paw clasping scores. In summary, these results suggest that IGF-1 has a protective role against HD-associated impaired glucose tolerance, by enhancing blood insulin levels. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Experimental Neurology
volume
231
pages
314 - 319
publisher
Academic Press
external identifiers
  • wos:000295108800015
  • pmid:21763311
  • scopus:80052520685
ISSN
0014-4886
DOI
10.1016/j.expneurol.2011.06.016
language
English
LU publication?
yes
id
7f40f7d6-b4b8-4cff-b445-363685f3379d (old id 2058572)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21763311?dopt=Abstract
date added to LUP
2011-08-01 13:15:40
date last changed
2017-10-01 04:57:35
@article{7f40f7d6-b4b8-4cff-b445-363685f3379d,
  abstract     = {Huntington's disease (HD) is the most prevalent polyglutamine expansion disorder. HD is caused by an expansion of CAG triplet in the huntingtin (HTT) gene, associated with striatal and cortical neuronal loss. Central and peripheral metabolic abnormalities and altered insulin-like growth factor-1 (IGF-1) levels have been described in HD. Thus, we hypothesized that restoration of IGF-1-mediated signaling pathways could rescue R6/2 mice from metabolic stress and behavioral changes induced by polyglutamine expansion. We analyzed the in vivo effect of continuous peripheral IGF-1 administration on diabetic parameters, body weight and motor behavior in the hemizygous R6/2 mouse model of HD. We used 9week-old and age-matched wild-type mice, subjected to continuously infused recombinant IGF-I or vehicle, for 14days. IGF-1 treatment prevented the age-related decrease in body weight in R6/2 mice. Although blood glucose levels were higher in R6/2 mice, they did not reach a diabetic state. Even though, IGF-1 ameliorated poor glycemic control in HD mice. This seemed to be associated with a decrease in blood insulin levels in R6/2 mice, which was increased following IGF-1 infusion. Similarly, blood IGF-1 levels decreased during aging in both wild-type and R6/2 mice, being significantly improved upon its continuous infusion. Although no significant differences were found in motor function in R6/2-treated mice, IGF-1 treatment highly improved paw clasping scores. In summary, these results suggest that IGF-1 has a protective role against HD-associated impaired glucose tolerance, by enhancing blood insulin levels.},
  author       = {Duarte, Ane and Petit, Géraldine and Ranganathan, Srikanth and Li, Jia-Yi and Oliveira, C R and Brundin, Patrik and Björkqvist, Maria and Rego, A C},
  issn         = {0014-4886},
  language     = {eng},
  pages        = {314--319},
  publisher    = {Academic Press},
  series       = {Experimental Neurology},
  title        = {IGF-1 protects against diabetic features in an in vivo model of Huntington's disease.},
  url          = {http://dx.doi.org/10.1016/j.expneurol.2011.06.016},
  volume       = {231},
  year         = {2011},
}