a whole-body model for glycogen regulation reveals a critical role for substrate cycling in maintaining blood glucose homeostasis糖原规定的全身模型揭示了一个衬底自行车在维持血糖稳态的关键作用.pdfVIP

A Whole-Body Model for Glycogen Regulation Reveals a Critical Role for Substrate Cycling in Maintaining Blood Glucose Homeostasis 1,2 3 4 2 1,2,5 Ke Xu , Kevin T. Morgan , Abby Todd Gehris , Timothy C. Elston *, Shawn M. Gomez * 1 Department of Biomedical Engineering, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America, 2 Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America, 3 Old Dogs in Training, Carrboro, North Carolina, United States of America, 4 Department of Mathematics, Broome Community College, Binghamton, New York, United States of America, 5 Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America Abstract Timely, and sometimes rapid, metabolic adaptation to changes in food supply is critical for survival as an organism moves from the fasted to the fed state, and vice versa. These transitions necessitate major metabolic changes to maintain energy homeostasis as the source of blood glucose moves away from ingested carbohydrates, through hepatic glycogen stores, towards gluconeogenesis. The integration of hepatic glycogen regulation with extra-hepatic energetics is a key aspect of these adaptive mechanisms. Here we use computational modeling to explore hepatic glycogen regulation under fed and fasting conditions in the context of a whole-body model. The model was validated against previous experimental results concerning glycogen phosphorylase a (active) and glycogen synthase a dynamics. The model qualitatively reproduced physiological changes that occur dur