A Local Counter-Regulatory Motif Modulates the Global Phase of Hormonal Oscillations

TL;DR

This paper uncovers a specific intra-islet interaction motif involving alpha, beta, and delta cells that modulates hormonal oscillations, balancing hormone secretion and synchronization for glucose regulation.

Contribution

It identifies a unique local interaction motif that controls hormonal oscillation phases and synchronization in pancreatic islets, revealing a new regulatory mechanism.

Findings

The motif reduces wasteful hormone interactions.

It enhances or suppresses hormone synchronization depending on glucose levels.

The interaction motif improves controllability of hormonal network dynamics.

Abstract

Counter-regulatory elements maintain dynamic equilibrium ubiquitously in living systems. The most prominent example, which is critical to mammalian survival, is that of pancreatic {\alpha} and {\beta} cells producing glucagon and insulin for glucose homeostasis. These cells are not found in a single gland but are dispersed in multiple micro-organs known as the islets of Langerhans. Within an islet, these two reciprocal cell types interact with each other and with an additional cell type: the {\delta} cell. By testing all possible motifs governing the interactions of these three cell types, we found that a unique set of positive/negative intra-islet interactions between different islet cell types functions not only to reduce the superficially wasteful zero-sum action of glucagon and insulin but also to enhance/suppress the synchronization of hormone secretions between islets under high/normal glucose conditions. This anti-symmetric interaction motif confers effective controllability for network (de)synchronization.