Author:
Saadati Maryam,Jamali Yousef
Abstract
AbstractType 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.
Publisher
Springer Science and Business Media LLC
Cited by
9 articles.
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