Effects of morphological and functional heterogeneities on the intracellular Ca2+ signals in coupled pancreatic beta cells


  • Gerardo Jorge Felix-Martinez* Universidad Autonoma Metropolitana
  • I. Morales-Reyes
  • J. R. Godinez-Fernandez


The Islets of Langerhans are mainly composed of insulin-secreting pancreatic ОІ-cells, glucagon-secreting О±-cells and somatostatin-secreting Оґ-cells[1]. At the cellular level, secretion of these hormones takes place through a common mech- anism involving glucose metabolism, electrical activity and Ca2+-handling[2]. In addition, pancreatic hormone secretion is regulated by intra-islet interactions including paracrine and autocrine signals, as well as electrical coupling mediated by gap junctions between ОІ-cells[3].

Electrical coupling between ОІ-cells has been previously studied both theo- retically and experimentally. In these studies, it was shown that ОІ-cell coupling is essential for the synchronized release of insulin[1]. In addition, it was demon- strated that the lack of functional gap junctions leads to impaired pulsatile insulin secretion due to uncoordinated Ca2+ oscillations[4].

In this work we used a computational model to assess the effect of morpho- logical and functional heterogeneities in the islet ОІ-cells (including differences in cell sizes, ОІ-cell interconnectivity and electrophysiological and Ca2+ buffering properties) on the Ca2+ signal produced in the cytosol, ultimately related to the secretory response of the islet ОІ-cells.


Farnsworth NL, Benninger RKP. New insights into the role of connexins in pancreatic islet function and diabetes. FEBS letters 2014; 588:127887.

Henquin JC, Ravier MA, Nenquin M, Jonas JC, Gilon P. Hierarchy of the beta-cell signals controlling insulin secretion. Eur J Clin Invest 2003; 33:74250.

Rutter GA, Hodson DJ. Minireview: Intraislet Regulation of Insulin Secre- tion in Humans. Molecular Endocrinology 2013; 27:198495.

Head, W. Steven, et al. Connexin-36 gap junctions regulate in vivo first- and second-phase insulin secretion dynamics and glucose tolerance in the conscious mouse. Diabetes 61.7 (2012): 1700-1707.






Conference Contributions