Network theory provides tools for quantifying communication within heterogeneous biological systems. Calcium-based imaging is a common technique used to analyze cellular dynamics and create functional networks. However, the use of functional networks in understanding the underlying biological structure, formed by physical connections, has not been well investigated. The islet of Langerhans is a biological system with relatively simple architecture that affords the opportunity for high-fidelity experimental and computation analysis, making it an ideal system to answer biological network theory-based questions. Here, we analyze both experimental and computational models of the islet to quantify the relationship between the gap junction structural network and functional synchronization networks. We show that functional networks poorly reflect gap junction structure. Instead, they indicate intrinsic factors driving excitability, such as cellular metabolism. This surprising finding provides a new interpretation of functional networks within biological systems.