Comprehensive Diabetes Center, University of Alabama at Birmingham, Birmingham, Alabama.
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
Am J Physiol Endocrinol Metab. 2019 Oct 1;317(4):E723-E730. doi: 10.1152/ajpendo.00122.2019. Epub 2019 Aug 13.
Pancreatic beta-cell death is a major factor in the pathogenesis of type 1 diabetes (T1D), but straightforward methods to measure beta-cell loss in humans are lacking, underlining the need for novel biomarkers. Using studies in INS-1 cells, human islets, diabetic mice, and serum samples of subjects with T1D at different stages, we have identified serum miR-204 as an early biomarker of T1D-associated beta-cell loss in humans. MiR-204 is a highly enriched microRNA in human beta-cells, and we found that it is released from dying beta-cells and detectable in human serum. We further discovered that serum miR-204 was elevated in children and adults with T1D and in autoantibody-positive at-risk subjects but not in type 2 diabetes or other autoimmune diseases and was inversely correlated with remaining beta-cell function in recent-onset T1D. Thus, serum miR-204 may provide a much needed novel approach to assess early T1D-associated human beta-cell loss even before onset of overt disease.
胰岛β细胞死亡是 1 型糖尿病（T1D）发病机制的一个主要因素，但目前缺乏直接测量人类β细胞损失的方法，这凸显了对新型生物标志物的需求。通过 INS-1 细胞、人胰岛、糖尿病小鼠以及不同阶段 T1D 患者的血清样本研究，我们发现血清 miR-204 是人类 T1D 相关β细胞损失的早期生物标志物。miR-204 是人类β细胞中高度富集的 microRNA，我们发现它是从濒死的β细胞中释放出来的，并可在人血清中检测到。我们还发现，血清 miR-204 在 T1D 患儿和成人以及自身抗体阳性的高危人群中升高，但在 2 型糖尿病或其他自身免疫性疾病中不升高，并且与新发 T1D 患者β细胞功能的剩余情况呈负相关。因此，血清 miR-204 可能为评估人类β细胞损失提供一种急需的新方法，甚至可以在明显疾病出现之前评估早期 T1D 相关的β细胞损失。
