Scientific Reports (May 2021)

The effects of beta-cell mass and function, intercellular coupling, and islet synchrony on $${\text {Ca}}^{2+}$$ Ca 2 + dynamics

  • Maryam Saadati,
  • Yousef Jamali

DOI
https://doi.org/10.1038/s41598-021-89333-x
Journal volume & issue
Vol. 11, no. 1
pp. 1 – 14

Abstract

Read online

Abstract Type 2 diabetes (T2D) is a challenging metabolic disorder characterized by a substantial loss of $$\beta $$ β -cell mass and alteration of $$\beta $$ β -cell function in the islets of Langerhans, disrupting insulin secretion and glucose homeostasis. The mechanisms for deficiency in $$\beta $$ β -cell mass and function during the hyperglycemia development and T2D pathogenesis are complex. To study the relative contribution of $$\beta $$ β -cell mass to $$\beta $$ β -cell function in T2D, we make use of a comprehensive electrophysiological model of human $$\beta $$ β -cell clusters. We find that defect in $$\beta $$ β -cell mass causes a functional decline in single $$\beta $$ β -cell, impairment in intra-islet synchrony, and changes in the form of oscillatory patterns of membrane potential and intracellular $${\text {Ca}}^{2+}$$ Ca 2 + concentration, which can lead to changes in insulin secretion dynamics and in insulin levels. The model demonstrates a good correspondence between suppression of synchronizing electrical activity and published experimental measurements. We then compare the role of gap junction-mediated electrical coupling with both $$\beta $$ β -cell synchronization and metabolic coupling in the behavior of $${\text {Ca}}^{2+}$$ Ca 2 + concentration dynamics within human islets. Our results indicate that inter- $$\beta $$ β -cellular electrical coupling depicts a more important factor in shaping the physiological regulation of islet function and in human T2D. We further predict that varying the whole-cell conductance of delayed rectifier $$\text {K}^{+}$$ K + channels modifies oscillatory activity patterns of $$\beta $$ β -cell population lacking intercellular coupling, which significantly affect $${\text {Ca}}^{2+}$$ Ca 2 + concentration and insulin secretion.