A Generic Integrated Physiologically based Whole‐body Model of the Glucose‐Insulin‐Glucagon Regulatory System
Tóm tắt
Models of glucose metabolism are a valuable tool for fundamental and applied medical research in diabetes. Use cases range from pharmaceutical target selection to automatic blood glucose control. Standard compartmental models represent little biological detail, which hampers the integration of multiscale data and confines predictive capabilities. We developed a detailed, generic physiologically based whole‐body model of the glucose‐insulin‐glucagon regulatory system, reflecting detailed physiological properties of healthy populations and type 1 diabetes individuals expressed in the respective parameterizations. The model features a detailed representation of absorption models for oral glucose, subcutaneous insulin and glucagon, and an insulin receptor model relating pharmacokinetic properties to pharmacodynamic effects. Model development and validation is based on literature data. The quality of predictions is high and captures relevant observed inter‐ and intra‐individual variability. In the generic form, the model can be applied to the development and validation of novel diabetes treatment strategies.
Từ khóa
Tài liệu tham khảo
International‐Diabetes‐Federation, 2011, IDF Diabetes Atlas
Sorensen J.T., 1985, A Physiologic Model of Glucose Metabolism in Man and its Use to Design and Assess Improved Insulin Therapies for Diabetes
Dalla Man C., 2006, Mixed meal simulation model of glucose‐insulin system, Conf. Proc. IEEE Eng. Med. Biol. Soc., 1, 307
Markakis M.G., 2008, Computational study of an augmented minimal model for glycaemia control, Conf. Proc. IEEE Eng. Med. Biol. Soc., 2008, 5445
Bottaro D.P., 1989, Insulin receptor recycling in vascular endothelial cells. Regulation by insulin and phorbol ester, J. Biol. Chem., 264, 5916, 10.1016/S0021-9258(18)83637-7
Gorden P., 1989, Biosynthesis and regulation of the insulin receptor, Yale J. Biol. Med., 62, 521
Services BT.SB Model Suite 5.1.4 – users manual. (2012).