Beneficial effects of intercellular interactions between pancreatic islet cells in blood glucose regulation

TL;DR

This study develops a mathematical model to analyze how intercellular interactions within pancreatic islets contribute to blood glucose regulation, revealing their roles in stabilizing glucose levels and optimizing hormone secretion.

Contribution

The paper introduces a novel mathematical model that explicitly incorporates intercellular chemical interactions and cell-to-cell variability in pancreatic islets.

Findings

Intercellular interactions stabilize glucose levels after perturbation.

Delta-cell inhibition prevents wasteful hormone co-secretion.

Glucose response of insulin is enhanced at high glucose levels.

Abstract

Glucose homeostasis is controlled by the islets of Langerhans which are equipped with alpha-cells increasing the blood glucose level, beta-cells decreasing it, and delta-cells the precise role of which still needs identifying. Although intercellular communications between these endocrine cells have recently been observed, their roles in glucose homeostasis have not been clearly understood. In this study, we construct a mathematical model for an islet consisting of two-state alpha-, beta-, and delta-cells, and analyze effects of known chemical interactions between them with emphasis on the combined effects of those interactions. In particular, such features as paracrine signals of neighboring cells and cell-to-cell variations in response to external glucose concentrations as well as glucose dynamics, depending on insulin and glucagon hormone, are considered explicitly. Our model predicts three possible benefits of the cell-to-cell interactions: First, the asymmetric interaction between alpha- and beta-cells contributes to the dynamic stability while the perturbed glucose level recovers to the normal level. Second, the inhibitory interactions of delta-cells for glucagon and insulin secretion prevent the wasteful co-secretion of them at the normal glucose level. Finally, the glucose dose-responses of insulin secretion is modified to become more pronounced at high glucose levels due to the inhibition by delta-cells. It is thus concluded that the intercellular communications in islets of Langerhans should contribute to the effective control of glucose homeostasis.