A multi-scale in silico mouse model for insulin resistance and humanoid type 2 diabetes _Validation_data

Insulin resistance (IR) causes compensatory insulin production, which in humans eventually progresses to beta-cell failure and type 2 diabetes (T2D). This disease progression involves multi-scale processes, ranging from intracellular signaling to organ-organ and whole-body level regulations, on timescales from minutes to years. T2D progression is commonly studied using overfed and genetically modified rodents. However, rodents do not exhibit human T2D progression, with IR-driven beta-cell failure, and available multi-scale data is too complex to fully comprehend using traditional analysis. To help resolve these issues, we here present an in silico mouse model. This is the first mathematical model that simultaneously explains multi-scale mouse IR data on all three levels – cells, organs, body – ranging from minutes to months. The model correctly predicts new independent multi-scale validation data and provides insights into non-measured processes. Finally, we present a humanoid in silico mouse exhibiting disease progression from IR to IR-driven T2D. Presented here is the dataset used for model validation. The dataset contains bodyweight and glucose tolerance test (IPGTT) data for an eight week HFD intervention with corresponding control using male C57BL/6J mice胰岛素抵抗（Insulin resistance, IR）可引发代偿性胰岛素分泌，在人类中最终会进展为β细胞衰竭与2型糖尿病（type 2 diabetes, T2D）。该疾病进程涵盖多尺度生理过程，其尺度范围从细胞内信号通路，延伸至器官间交互与全身层面的调控，时间跨度从数分钟至数年。目前针对2型糖尿病进程的研究，通常采用过食喂养联合转基因改造的啮齿类动物作为实验模型，但啮齿类动物并不会呈现人类2型糖尿病的典型进展模式——即由胰岛素抵抗驱动的β细胞衰竭；且现有的多尺度数据集过于复杂，难以通过传统分析手段实现完全解析。为解决上述问题，本研究构建了一款计算机模拟（in silico）小鼠模型。这是首个可同时覆盖细胞、器官、全身三个尺度，阐释小鼠胰岛素抵抗多尺度数据的数学模型，时间跨度从数分钟至数月。该模型可准确预测全新的独立多尺度验证数据集，并为未被直接检测的生理过程提供研究视角。最后，本研究还构建了一款类人计算机模拟（in silico）小鼠，可完整展现从胰岛素抵抗到胰岛素抵抗驱动型2型糖尿病的疾病进程。本文所附的即为用于该模型验证的数据集。该数据集包含雄性C57BL/6J小鼠在8周高脂饮食（high-fat diet, HFD）干预组及其对应的对照组中的体重与腹腔葡萄糖耐量试验（intraperitoneal glucose tolerance test, IPGTT）数据。