Primary cilia as platforms for islet neurotransmitter signaling

Pancreatic islets maintain glucose homeostasis through the coordinated secretion of hormones and, notably, neurotransmitters. While islet innervation has long been recognized as essential for development and function, the source of these neuromodulators is variable and so is their signaling. Islet α and β cells express a broad repertoire of receptors for neurotransmitters such as acetylcholine, glutamate, GABA, and catecholamines. Emerging evidence reveals an additional layer of regulatory complexity, as a subset of these receptors localize to the primary cilium, a sensory organelle that functions as a specialized signaling hub. Disruption of primary cilia on β cells impairs glucose homeostasis in mice, and human ciliopathies commonly feature metabolic dysfunction. In this review, we synthesize recent findings on neurotransmitter signaling within the islet, with a focus on pathways that converge on the primary cilium. We discuss how compartmentalized signaling via cilia-enriched receptors represents a new dimension of islet cell regulation and offer a perspective on how targeting these ciliary pathways may provide future research directions for modulating α- and β-cell function in diabetes.