Mathematical model of calcium-dependent glycemic control components in hepatocytes
Oksana M. Tilinova,1 Arina V. Martyshina,1 Irina V. Dokukina,1 Sofia I. Kisil,2 Mikhail V. Yamashev,3 Eugene A. Grachev,3 1 Sarov Physical and Technical Institute, National Research Nuclear University MEPhI, Sarov, Russia 2 Biology department, Lomonosov Moscow State University, Moscow, Russia 3 Physics department, Lomonosov Moscow State University, Moscow, Russia
Abstract
The liver is the most important organ of the human glycemic control system. Depending on the state of the body – food intake or hunger – hepatocytes are able to either store excess glucose in glycogen, or release glucose into the blood, receiving it from glycogen stores or as a result of the gluconeogenesis process.
Active calcium signaling is triggered in the hepatocyte in a state of starvation of the body in response to the effect of glucagon on the cell. An increase in the concentration of calcium ions in the cytosol stimulates the processes of glycogenolysis and gluconeogenesis. In the postprandial state both processes are normally blocked by insulin and, in addition to storing glucose in glycogen, some glucose is metabolized into fatty acids as a result of glycolysis and lipogenesis, followed by the formation of very low-density lipoproteins and their release into the blood [1].
In this work we construct a new mathematical model that allows us to take into consideration all the described processes. The model is based on the ODE system. The model takes into account the complex dynamics of close contacts of mitochondria with the endoplasmic reticulum indirectly [2], [3]. The model considers both the normal mode of cell operation and the pathological state of hepatocyte resistance insulin. Modeling results allow us to draw certain conclusions about the mechanisms of the development of hepatocyte function pathology.
References:
1. Samuel, V., Shulman, G., 2016. The pathogenesis of insulin resistance: integrating signaling pathways and substrate flux. J. Clin. Invest. 126 (1), 12–22.
https://doi.org/10.1172/JCI77812
2. Theurey, P., Tubbs, E., Vial, G., Jacquemetton, J., Bendridi, N., Chauvin, M.A., Alam, M.R., Le Romancer, M., Vidal, H., Rieusset, J., 2016. Mitochondria-associated endoplasmic reticulum membranes allow adaptation of mitochondrial metabolism to glucose availability in the liver. J. Mol. Cell Biol. 8 (2), 129–143.
https://doi.org/10.1093/jmcb/mjw004
3. Dokukina, I.V., Yamashev, M.V., Samarina, E.A., Tilinova, O.M., Grachev, E.A., 2021. Calcium-dependent insulin resistance in hepatocytes: mathematical model. J. Theor. Biol. 522, 110684
https://doi.org/10.1016/j.jtbi.2021.110684
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Oksana Tilinova
Sarov Physical and Technical Institute, National Research Nuclear University MEPhI
Russia
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