Multiscale Trajectory Analysis and Snapshot 3D Microscopy Studies Elucidate Functional Consequences of Heterogeneous Insulin Granule Trafficking

Challenges in the study of intracellular insulin granules arise from heterogeneous and stochastic influences on the observed transport in beta-cells. Through fluorescence microscopy and single particle tracking, the dynamics of individual granules can be studied individually and as an ensemble to identify characteristic subpopulations of dynamics. Characteristic dynamics observed in intracellular transport, at steady-state and at glucose stimulation, indicate functionally distinct pools that have different mobilization criteria for glucose-stimulated insulin secretion. Elucidation of physical mechanisms underlying biphasic insulin secretion must be inferred from detailed study of intracellular insulin dynamics and the environmental contributions to the transport. Identification of functionally distinct dynamics and their physical mechanisms could provide insight into potential beta-cell secretion deficiency and ultimately, mechanisms of beta-cell dysfunction defects related to diabetes.