A multi-scale in silico mouse model for insulin resistance and humanoid type 2 diabetes _Validation_data
Description
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
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Steps to reproduce
Animals and high fat diet intervention Short-term overfeeding was carried out as previously described (2, 20, 42). Male C57BL/6J mice (Taconic, Ry, Denmark) were used at 8-9 weeks of age. Animals were on a 12 h light cycle with non-restricted food and water. Groups of animals (n=6-10 animals/group) were fed either chow or HFD (D12492 60 E% fat content; Research Diets, New Brunswick, NJ, USA) for 6-8 weeks. Body weight (BW) of individual animals were measured weekly. Animals and intraperitoneal glucose tolerance test A subset of animals (n=10/group) were subjected to intraperitoneal glucose tolerance test (IPGTT). In short, mice fasted overnight (12 h) were injected intraperitoneally with glucose (50 mg/mouse) and serum samples were collected at indicated times. Blood glucose levels were measured (Accu-Chek, Lund, Sweden), and insulin levels were assayed using ELISA (Mercodia, Uppsala, Sweden). The supplier´s protocol was followed with an adjustment of the amount of sample volume (5µL of each sample) and the incubation time (30 min at room temperature). All animal procedures were approved by the Malmö/Lund Committee for Animal Experiment Ethics, Lund, Sweden, and were carried out in accordance with the relevant guidelines and regulations.
Institutions
- Linkopings universitet
- Lunds Universitet