Contents lists available at ScienceDirect Journal of Thermal Biology journal homepage: www.elsevier.com/locate/jtherbio Computational modeling of the effect of temperature variations on human pancreatic β-cell activity Sajjad Farashi a , Pezhman Sasanpour a,b, ⁎ , Hashem Rafii-Tabar a, ⁎⁎ a Department of Medical Physics & Biomedical Engineering, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran b Computational Nano-Bioelectromagnetics Research Group, School of Nano-Science, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran ARTICLE INFO Keywords: Computational modeling Temperature effect Pancreatic β-cell Mathematical modeling Q10 coefficient ABSTRACT The effect of temperature variations on the pancreatic β-cell activity and the role of different model compart- ments in temperature sensing have been investigated using a computational modeling approach. The results of our study show that temperature variations by several degrees can change the dynamical states of the β-cell system. In addition, temperature variations can alter the characteristic features of the membrane voltage, which correlates with insulin secretion. Simulation results show that the ion channels such as the L-type calcium, the hERG potassium, sodium channels and the glycolysis pathway are the possible sites for sensing temperature variation. Results indicate that for a small temperature change, even though the frequency and amplitude of electrical activity are altered, the area under the membrane potential curve remains almost unchanged, which implies the existence of a thermoregulatory mechanism for preserving the amount of insulin secretion. Furthermore, the computational analysis shows that the β-cell electrical activity exhibits a bursting pattern in physiological temperature (37 °C) while in vitro studies reported almost the spiking activity at lower tempera- tures. Since hormone-secreting systems work more efficient in bursting mode, we propose that the pancreatic β- cell works better in the physiological temperature compared with the reference temperature (33 °C). 1. Introduction Temperature has a substantial effect on cell functions. The compo- sition of a cell membrane and the chemical reactions unfolding inside the cell may undergo transformation due to temperature variations (Quinn, 1988). The temperature variation can also directly affect sev- eral kinds of receptors and ion channels (Liman, 2006), glycolytic flux (Cruz et al., 2012; Postmus et al., 2008), enzymatic activity (Daniel et al., 2008), kinetics of ion channels (Collins and Rojas, 1982; Kimitsuki and Komune, 2013; Rosen, 2001; Sterratt, 2014b), the Nernst equilibrium potential of ion channels, half-maximal activation voltage along the channel (Yang and Zheng, 2014) and the membrane potential (Buzatu, 2009). The way that temperature affects cell functions and the underlying mechanisms have gained special attention in biology. There are several studies regarding the effect of temperature on cellular compartments and functions. Rosen showed that the inactiva- tion time constant of sodium channels were linearly temperature sen- sitive, while the activation time constant exhibited a nonlinear response to temperature, possibly due to the membrane structural changes in the thermotropic phase transition (Rosen, 2001). Milburn et al. reported the increase of sodium channel's conductance due to the temperature rise through the increasing of channel energy barrier at higher tem- peratures (Milburn et al., 1995). The conductance-temperature re- lationship in octopus cells of the mammalian ventral cochlear nucleus (VCN) showed that temperature changed the conductance of K + channels through affecting the kinetics and hyperpolarization-activated current (Cao and Oertel, 2005). Another study showed the temperature dependence of amylase secretion from the pancreas which might be possibly due to the alteration of the physical state of the membrane (Beaudoin and Mercier, 1980). Mair et al. used the sensitivity of phosphofructokinase and glyceraldehyde-3-phosphate dehydrogenase phases of glycolysis to temperature for controlling chemical reactions in the cellular systems (Mair et al., 2005). Chemin et al. showed that protein kinase in the specific temperature range (30–37 °C) increased the flux of low voltage-activated Cav3 T-type calcium channels in mammalian cell lines (Chemin et al., 2007). The fundamental function of the pancreatic β-cell is insulin secre- tion. There are several studies which report the temperature sensitivity of insulin granule secretion. Ivarsson et al. showed that reducing the temperature could reduce the frequency and velocity of insulin granule https://doi.org/10.1016/j.jtherbio.2018.05.006 Received 30 January 2018; Received in revised form 23 May 2018; Accepted 24 May 2018 ⁎ Corresponding author at: Department of Medical Physics & Biomedical Engineering, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. ⁎⁎ Corresponding author. E-mail addresses: pesasanpour@sbmu.ac.ir (P. Sasanpour), rafii-tabar@nano.ipm.ac.ir (H. Rafii-Tabar). Journal of Thermal Biology 75 (2018) 69–80 Available online 26 May 2018 0306-4565/ © 2018 Elsevier Ltd. All rights reserved. T