胰岛β细胞亚群标志物FTL调控胰岛β细胞糖代谢的作用机制研究

Along with the continuous increase of the prevalence of diabetes, disorder of pancreatic glucose metabolism has become an important clinical problem. Mechanisms and regulations of the factors, which play key roles in glucose metabolism of β cells, have become new research focus. The applicant is committed to studies regarding the genetic regulatory mechanisms of β cells in a long history. Through the single-cell transcriptome data sequenced in islets of donors from healthy children, adults and type 2 diabetic patients, we found that FTL was the marker of islet β cell subgroups and was closely related to β cell dysfunction in type 2 diabetes. On this basis, we will generate pancreatic β cell specific Ftl transgenic mouse models and continue to explore the precise function and regulation mechanism of Ftl in the glucose metabolism of β cells, and further elaborate the regulatory network that influences the proliferation and function of β cells. In addition, our studies aim to clarify the effects of small molecule drugs targeting Ftl target gene in diabetic mouse model and ultimately provide innovative and more effectively preventive approaches and diagnostic markers as well as therapeutic targets, and provide scientific evidence for preventing and slowing the progression of glucose disorder.

随着糖尿病患病率不断增高，胰岛糖代谢紊乱症候群已成为重要临床问题。调控胰岛β细胞糖代谢中发挥关键作用的因子及其作用机制已成为新的关注热点。申请者长期致力于胰岛β细胞遗传与表观因素的调控机制研究，通过健康成人及2型糖尿病患者胰岛单细胞测序的基因表达图谱，发现了胰岛β细胞亚群标志基因铁蛋白轻链(FTL)与2型糖尿病的胰岛β细胞功能损伤密切联系。在此基础上，本项目将建立胰岛β细胞特异性FTL转基因小鼠模型，深入探索FTL在胰岛β细胞糖代谢中的精确功能与调控机制，进一步阐述影响胰岛β细胞增殖和功能的调控网络。最终提供新的更有效的胰岛糖代谢紊乱的预防途径、诊断标志物与治疗靶点，为预防和延缓胰岛糖代谢紊乱提供科学依据。

随着糖尿病患病率不断增高，胰岛糖代谢紊乱症候群已成为重要临床问题。调控胰岛β细胞糖代谢中发挥关键作用的因子及其作用机制已成为新的关注热点。本研究通过健康成人及2型糖尿病患者胰岛单细胞测序的基因表达图谱，发现了胰岛β细胞亚群标志基因铁蛋白轻链(FTL)与2型糖尿病的胰岛β细胞功能损伤密切联系。在此基础上，本项目利用条件性转基因动物模型、MIN6细胞系和原代胰岛细胞等多种研究技术平台，深入探索FTL在胰岛β细胞糖代谢通过精确功能与调控机制，进一步阐述let7b-5p-Ftl影响胰岛β细胞增殖和功能的调控网络。最终提供新的更有效的胰岛糖代谢紊乱的预防途径、诊断标志物与治疗靶点，为预防和延缓胰岛糖代谢紊乱提供科学依据。