Institute of Biotechnology, University of Helsinki, Finland.
Division of Pharmaceutical Biosciences, Centre for Drug Research, University of Helsinki, Finland.
Sci Rep. 2016 Jun 30;6:29058. doi: 10.1038/srep29058.
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.
中脑星形胶质细胞衍生神经营养因子（MANF）最近被证明对小鼠胰岛β细胞的存活和增殖至关重要，MANF 的缺失导致糖尿病。本研究旨在确定循环 MANF 的浓度是否与人类 1 型糖尿病（T1D）的临床表现相关。尚未研究 T1D 中的 MANF 表达或血清中的 MANF 水平。我们开发了一种用于 MANF 的酶联免疫吸附测定（ELISA），并测量了 186 名新诊断的儿童和青少年以及 20 名患有长期 T1D 的成年人以及年龄匹配的对照者的血清 MANF 浓度。在健康对照组中，平均血清 MANF 浓度为 7.0ng/ml。在接近 T1D 诊断的 1-9 岁儿童中发现了高浓度的 MANF。增加的 MANF 浓度与糖尿病预测性自身抗体无关，并且针对 MANF 的自身抗体极为罕见。与 MANF 浓度适中的患者相比，MANF 血清浓度明显升高的患者的 C 肽水平较低。我们的数据表明，血清中 MANF 浓度的升高与儿童 T1D 的临床表现相关，但增加的具体机制仍不清楚。
