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Increased circulating concentrations of mesencephalic astrocyte-derived neurotrophic factor in children with type 1
Emilia Galli1,2, Taina Härkönen3,4, Markus T Sainio1
1Institute of Biotechnology, University of Helsinki, Finland.
Abstract:
Mesencephalic astrocyte-derived neurotrophic factor (MANF) was recently shown to be essential for the survival and proliferation of pancreatic β-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.
Insights
Serum levels of Mesencephalic astrocyte-derived neurotrophic factor (MANF) are elevated in children newly diagnosed with type 1 diabetes (T1D). This increase in MANF may be linked to T1D manifestation but requires further investigation into its underlying mechanisms.
Area of Science:
- Endocrinology
- Immunology
- Neuroscience
Background:
- Mesencephalic astrocyte-derived neurotrophic factor (MANF) is crucial for pancreatic beta-cell survival and proliferation.
- MANF deficiency in mice leads to diabetes, suggesting a potential role in human diabetes.
- Circulating MANF levels in human type 1 diabetes (T1D) have not been previously investigated.
Purpose of the Study:
- To determine if serum MANF concentrations correlate with the clinical presentation of human T1D.
- To establish a method for quantifying MANF in human serum.
Main Methods:
- Development of an enzyme-linked immunosorbent assay (ELISA) for MANF.
- Measurement of serum MANF concentrations in 186 newly diagnosed T1D children/adolescents, 20 long-term T1D adults, and age-matched controls.
- Analysis of MANF concentrations in relation to diabetes-predictive autoantibodies, anti-MANF autoantibodies, and C-peptide levels.
Main Results:
- Mean serum MANF in healthy controls was 7.0 ng/ml.
- Significantly higher MANF concentrations were observed in children aged 1-9 years at the time of T1D diagnosis.
- Increased MANF levels were not linked to diabetes-predictive autoantibodies or anti-MANF autoantibodies.
- Patients with very high MANF serum levels exhibited lower C-peptide levels compared to those with moderate MANF concentrations.
Conclusions:
- Elevated serum MANF concentrations are associated with the clinical manifestation of T1D in children.
- The precise mechanism driving the increase in MANF during T1D remains unclear.
- Further research is needed to elucidate the role of MANF in T1D pathogenesis.
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