IGF-1 protects against diabetic features in an in vivo model of Huntington's disease
| Autor: | Ane Duarte, Géraldine H Petit, Maria Björkqvist, Patrik Brundin, Srikanth Ranganathan, Catarina R. Oliveira, Ana Cristina Rego, Jia-Yi Li |
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| Rok vydání: | 2011 |
| Předmět: |
Blood Glucose
medicine.medical_specialty Huntingtin Neurology Transgene medicine.medical_treatment Mice Transgenic Motor Activity Impaired glucose tolerance Mice Developmental Neuroscience Huntington's disease In vivo Internal medicine Glucose Intolerance medicine Animals Insulin Insulin-Like Growth Factor I business.industry Body Weight medicine.disease Peripheral Disease Models Animal Huntington Disease Endocrinology business |
| Zdroj: | Experimental Neurology. 231:314-319 |
| ISSN: | 0014-4886 |
| DOI: | 10.1016/j.expneurol.2011.06.016 |
| Popis: | 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 9 week-old and age-matched wild-type mice, subjected to continuously infused recombinant IGF-I or vehicle, for 14 days. 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. |
| Databáze: | OpenAIRE |
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