Increased circulating concentrations of mesencephalic astrocyte-derived neurotrophic factor in children with type 1 diabetes

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Galli , E , Harkonen , T , Sainio , M , Ustav , M , Toots , U , Urtti , A , Yliperttula , M , Lindahl , M , Knip , M , Saarma , M & Lindholm , P 2016 , ' Increased circulating concentrations of mesencephalic astrocyte-derived neurotrophic factor in children with type 1 diabetes ' , Scientific Reports , vol. 6 , 29058 . https://doi.org/10.1038/srep29058

Title: Increased circulating concentrations of mesencephalic astrocyte-derived neurotrophic factor in children with type 1 diabetes
Author: Galli, Emilia; Harkonen, Taina; Sainio, Markus; Ustav, Mart; Toots, Urve; Urtti, Arto; Yliperttula, Marjo; Lindahl, Maria; Knip, Mikael; Saarma, Mart; Lindholm, Paivi
Contributor: University of Helsinki, Institute of Biotechnology
University of Helsinki, Clinicum
University of Helsinki, Research Programs Unit
University of Helsinki, Faculty of Pharmacy
University of Helsinki, Faculty of Pharmacy
University of Helsinki, Institute of Biotechnology
University of Helsinki, Clinicum
University of Helsinki, Institute of Biotechnology
University of Helsinki, Institute of Biotechnology
Date: 2016-06-30
Language: eng
Number of pages: 11
Belongs to series: Scientific Reports
ISSN: 2045-2322
URI: http://hdl.handle.net/10138/164975
Abstract: Mesencephalic astrocyte-derived neurotrophic factor (MANF) was recently shown to be essential for the survival and proliferation of pancreatic beta-cells in mice, where deletion of MANF resulted in diabetes. The current study aimed at determining whether the concentration of circulating MANF is associated with the clinical manifestation of human type 1 diabetes (T1D). MANF expression in T1D or MANF levels in serum have not been previously studied. We developed an enzyme-linked immunosorbent assay (ELISA) for MANF and measured serum MANF concentrations from 186 newly diagnosed children and adolescents and 20 adults with longer-term T1D alongside with age-matched controls. In healthy controls the mean serum MANF concentration was 7.0 ng/ml. High MANF concentrations were found in children 1-9 years of age close to the diagnosis of T1D. The increased MANF concentrations were not associated with diabetes-predictive autoantibodies and autoantibodies against MANF were extremely rare. Patients with conspicuously high MANF serum concentrations had lower C-peptide levels compared to patients with moderate MANF concentrations. Our data indicate that increased MANF concentrations in serum are associated with the clinical manifestation of T1D in children, but the exact mechanism behind the increase remains elusive.
Subject: ENDOPLASMIC-RETICULUM STRESS
PANCREATIC BETA-CELLS
DOPAMINERGIC-NEURONS
GENERAL-POPULATION
INSULIN
MANF
INFLAMMATION
PROTEIN
DEATH
AUTOANTIBODIES
3111 Biomedicine
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