Randomness in the Hybrid Modeling and Simulation of Insulin Secretion Pathways in Pancreatic Islets

被引:0
作者
Pu, Yang [1 ]
Samuels, David C. [2 ]
Watson, Layne T. [1 ]
Cao, Yang [1 ]
机构
[1] Virginia Polytech Inst & State Univ, Dept Comp Sci, Blacksburg, VA 24061 USA
[2] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA
基金
美国国家卫生研究院; 美国国家科学基金会;
关键词
insulin secretion; mathematical modeling; hybrid model and simulation; stochastic dynamics; GLUCOSE-INDUCED OSCILLATIONS; EXACT STOCHASTIC SIMULATION; ELECTRICAL-ACTIVITY; MITOCHONDRIAL; GLYCOLYSIS; NETWORK; CELLS; CYCLE;
D O I
10.1109/TST.2015.7297743
中图分类号
TP [自动化技术、计算机技术];
学科分类号
0812 ;
摘要
Insulin secreted by pancreatic islet beta-cells is the principal regulating hormone of glucose metabolism. Disruption of insulin secretion may cause glucose to accumulate in the blood, and result in diabetes mellitus. Although deterministic models of the insulin secretion pathway have been developed, the stochastic aspect of this biological pathway has not been explored. The first step in this direction presented here is a hybrid model of the insulin secretion pathway, in which the delayed rectifying K+ channels are treated as stochastic events. This hybrid model can not only reproduce the oscillation dynamics as the deterministic model does, but can also capture stochastic dynamics that the deterministic model does not. To measure the insulin oscillation system behavior, a probability-based measure is proposed and applied to test the effectiveness of a new remedy.
引用
收藏
页码:441 / 452
页数:12
相关论文
共 35 条
[1]  
Arkin A, 1998, GENETICS, V149, P1633
[2]   Contribution of the endoplasmic reticulum to the glucose-induced [Ca2+]c response in mouse pancreatic islets [J].
Arredouani, A ;
Henquin, JC ;
Gilon, P .
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2002, 282 (05) :E982-E991
[3]   A simplified model for mitochondrial ATP production [J].
Bertram, Richard ;
Gram Pedersen, Morten ;
Luciani, Dan S. ;
Sherman, Arthur .
JOURNAL OF THEORETICAL BIOLOGY, 2006, 243 (04) :575-586
[4]   A mathematical study of the differential effects of two SERCA isoforms on Ca2+ oscillations in pancreatic islets [J].
Bertram, Richard ;
Arceo, Rudy C., II .
BULLETIN OF MATHEMATICAL BIOLOGY, 2008, 70 (05) :1251-1271
[5]   Interaction of glycolysis and mitochondrial respiration in metabolic oscillations of pancreatic islets [J].
Bertram, Richard ;
Satin, Leslie S. ;
Pedersen, Morten Gram ;
Luciani, Dan S. ;
Sherman, Arthur .
BIOPHYSICAL JOURNAL, 2007, 92 (05) :1544-1555
[6]   Adaptive explicit-implicit tau-leaping method with automatic tau selection [J].
Cao, Yang ;
Gillespie, Daniel T. ;
Petzold, Linda R. .
JOURNAL OF CHEMICAL PHYSICS, 2007, 126 (22)
[7]  
Cerasi E., 1992, Insulin, Molecular Biology to Pathology, P347
[8]   Integrative analysis of cell cycle control in budding yeast [J].
Chen, KC ;
Calzone, L ;
Csikasz-Nagy, A ;
Cross, FR ;
Novak, B ;
Tyson, JJ .
MOLECULAR BIOLOGY OF THE CELL, 2004, 15 (08) :3841-3862
[9]   An integrated model of cardiac mitochondrial energy metabolism and calcium dynamics [J].
Cortassa, S ;
Aon, MA ;
Marbán, E ;
Winslow, RL ;
O'Rourke, B .
BIOPHYSICAL JOURNAL, 2003, 84 (04) :2734-2755
[10]   Computer simulations reveal properties of the cell-cell signaling network at the shoot apex in Arabidopsis [J].
de Reuille, PB ;
Bohn-Courseau, I ;
Ljung, K ;
Morin, H ;
Carraro, N ;
Godin, C ;
Traas, J .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (05) :1627-1632