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Type 2 diabetes (T2D) is a challenging metabolic disorder characterized by asubstantial loss of $\beta$-cell mass and alteration of $\beta$-cell functionin the islets of Langerhans, disrupting insulin secretion and glucosehomeostasis. The mechanisms for deficiency in $\beta$-cell mass and functionduring the hyperglycemia development and T2D pathogenesis are complex. To studythe relative contribution of $\beta$-cell mass to $\beta$-cell function in T2D,we make use of a comprehensive electrophysiological model of human $\beta$-cellclusters. We find that defect in $\beta$-cell mass causes a functional declinein single $\beta$-cell, impairment in intra-islet synchrony, and changes in theform of oscillatory patterns of membrane potential and intracellular$\textrm{Ca}^{2+}$ concentration, which can lead to changes in insulinsecretion dynamics and in insulin levels. The model demonstrates a goodcorrespondence between suppression of synchronizing electrical activity andpublished experimental measurements. We then compare the role of gapjunction-mediated electrical coupling with both $\beta$-cell synchronizationand metabolic coupling in the behavior of $\textrm{Ca}^{2+}$ concentrationdynamics within human islets. Our results indicate that inter-$\beta$-cellularelectrical coupling depicts a more important factor in shaping thephysiological regulation of islet function and in human T2D. We further predictthat varying the whole-cell conductance of delayed rectifier $\textrm{K}^{+}$channels modifies oscillatory activity patterns of $\beta$-cell populationlacking intercellular coupling, which significantly affect $\textrm{Ca}^{2+}$concentration and insulin secretion.

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