Compartmentalized Nutrient and Hormone Sensing in β-Cells: the Role of Primary Cilia.

Pancreatic β-cells couple nutrient and hormone sensing to insulin release. Prevailing models depict the β-cell as a homogeneous metabolic unit, overlooking specialized subcellular compartments like the primary cilium. Primary cilia are sensory organelles that function as critical signaling hubs in pancreatic β-cells. Disrupting primary cilia causes diabetes, but the underlying mechanisms remain unclear. In this review, we critically assess evidence supporting the cilium's role in β-cells, including functional studies that implicate cilia in the control of cytosolic Ca2+ dynamics and exocytosis, molecular studies that identify key hormone receptors on β-cell cilia, and genetic data linking cilia gene perturbations with diabetes in humans and rodents. We argue that the evidence for an acute function in stimulus-secretion coupling is insufficient and outline the missing links required to define the cilium's precise signaling role, focusing on how it might detect glucose and hormonal inputs, generate an outgoing signal, and relay this information to the cell body to control insulin secretion. Resolving these questions will not only clarify a fundamental aspect of β-cell biology but may reveal principles of subcellular signaling relevant to physiology and disease in other organ systems.