Beta-cell Metabolic Activity Rather than Gap Junction Structure Dictates Subpopulations in the Islet Functional Network

Diabetes is caused by dysfunction of electrically coupled heterogeneous β-cells within the pancreatic islet. Functional networks have been used to represent cellular synchronization and study β-cells subpopulations, which play an important role in driving dynamics. The mechanism by which highly synchronized β-cell subpopulations drive islet function is not clear. We used experimental and computational techniques to investigate the relationship between functional networks, structural (gap-junction) networks, and underlying β-cell dynamics. Highly synchronized subpopulations in the functional network were differentiated by metabolic dynamics rather than structural coupling. Consistent with this, metabolic similarities were more predictive of edges in the islet functional network. Finally, removal of gap junctions, as occurs in diabetes, caused decreases in the efficiency and clustering of the functional network. These results indicate that metabolism rather than structure drives connections in the function network, deepening our interpretation of functional networks and the formation of functional sub-populations in dynamic tissues such as the islet.