Institute of Biotechnology CAS, 25250 Vestec, Czech Republic.
Department of Cell Biology, Faculty of Science, Charles University, 12843 Prague, Czech Republic.
Int J Mol Sci. 2021 Jun 23;22(13):6713. doi: 10.3390/ijms22136713.
Diabetes is a metabolic disease that involves the death or dysfunction of the insulin-secreting β cells in the pancreas. Consequently, most diabetes research is aimed at understanding the molecular and cellular bases of pancreatic development, islet formation, β-cell survival, and insulin secretion. Complex interactions of signaling pathways and transcription factor networks regulate the specification, growth, and differentiation of cell types in the developing pancreas. Many of the same regulators continue to modulate gene expression and cell fate of the adult pancreas. The transcription factor NEUROD1 is essential for the maturation of β cells and the expansion of the pancreatic islet cell mass. Mutations of the gene cause diabetes in humans and mice. However, the different aspects of the requirement of NEUROD1 for pancreas development are not fully understood. In this study, we investigated the role of NEUROD1 during the primary and secondary transitions of mouse pancreas development. We determined that the elimination of impairs the expression of key transcription factors for α- and β-cell differentiation, β-cell proliferation, insulin production, and islets of Langerhans formation. These findings demonstrate that the deletion altered the properties of α and β endocrine cells, resulting in severe neonatal diabetes, and thus, NEUROD1 is required for proper activation of the transcriptional network and differentiation of functional α and β cells.
糖尿病是一种代谢疾病，涉及胰腺中胰岛素分泌β细胞的死亡或功能障碍。因此，大多数糖尿病研究都旨在了解胰腺发育、胰岛形成、β细胞存活和胰岛素分泌的分子和细胞基础。信号通路和转录因子网络的复杂相互作用调节着发育中胰腺细胞类型的特化、生长和分化。许多相同的调节剂继续调节成年胰腺的基因表达和细胞命运。转录因子 NEUROD1 对于β细胞的成熟和胰腺胰岛细胞质量的扩张是必不可少的。基因的突变会导致人类和小鼠患上糖尿病。然而，对于 NEUROD1 在胰腺发育中的不同方面的要求还不完全清楚。在这项研究中，我们研究了 NEUROD1 在小鼠胰腺发育的原发性和次级转变过程中的作用。我们确定了 基因的缺失会损害α和β细胞分化、β细胞增殖、胰岛素产生和朗格汉斯岛形成的关键转录因子的表达。这些发现表明，缺失改变了α和β内分泌细胞的特性，导致严重的新生儿糖尿病，因此，NEUROD1 是正确激活转录网络和功能性α和β细胞分化所必需的。
