title: Serum insulin-like system alterations in patients with spinocerebellar ataxia type 3.
abstract: Spinocerebellar ataxias (SCAs) constitute a group of autosomal dominant neurodegenerative disorders with no current treatment. The insulin/insulin-like growth factor 1 (IGF-1) system (IIS) has been shown to play a role in the neurological dysfunction of SCAs and other polyglutamine disorders. We aimed to study the biomarker profile of serum IIS components in SCA3. We performed a case-control study with 46 SCA3 patients and 42 healthy individuals evaluating the peripheral IIS profile (insulin, IGF-1, IGFBP1 and 3) and the correlation with clinical, molecular, and neuroimaging findings. SCA3 patients presented lower insulin and IGFBP3 levels and higher insulin sensitivity (HOMA2), free IGF-I, and IGFBP1 levels when compared with controls. IGFBP-1 levels were directly associated with CAG expanded repeat length; IGF-1 was associated with the volumetries of specific brainstem regions on magnetic resonance imaging (MRI). Insulin levels and sensitivity were related to age at onset of symptoms. Our findings indicate an involvement of IIS components in SCA3 neurobiology and IGFBP-1 as a potential biomarker of the disease.
authors.affiliation: Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Jonas Alex Morales
authors.initials: JA
authors.lastname: Saute
authors.forename: Andrew Chaves Feitosa
authors.initials: AC
authors.lastname: da Silva
authors.forename: Alexandre Pastoris
authors.initials: AP
authors.lastname: Muller
authors.forename: Gisele
authors.initials: G
authors.lastname: Hansel
authors.forename: Alexandre Silva
authors.initials: AS
authors.lastname: de Mello
authors.forename: Fábio
authors.initials: F
authors.lastname: Maeda
authors.forename: Leonardo
authors.initials: L
authors.lastname: Vedolin
authors.forename: Maria Luiza
authors.initials: ML
authors.lastname: Saraiva-Pereira
authors.forename: Diogo Onofre
authors.initials: DO
authors.lastname: Souza
authors.forename: Javier
authors.initials: J
authors.lastname: Arpa
authors.forename: Ignacio
authors.initials: I
authors.lastname: Torres-Aleman
authors.forename: Luis Valmor Cruz
authors.initials: LV
authors.lastname: Portela
authors.forename: Laura Bannach
authors.initials: LB
authors.lastname: Jardim
mesh_terms: D000328:Adult; D000067699:Ataxin-3; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood*; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood*; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D017827:Machado-Joseph Disease / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics
chemical_list: C032231:IGFBP1 protein, human; C515497:IGFBP3 protein, human; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D007334:Insulin-Like Growth Factor I; C092341:ATXN3 protein, human; D000067699:Ataxin-3