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. 2022 Sep 23;8(38):eabq8486. doi: 10.1126/sciadv.abq8486

Fig. 4. Cilia motility is required for glucose-stimulated insulin secretion.

Fig. 4.

(A) Dual-color live imaging showing GFP-labeled transduced beta cells in whole islets labeled with Calbryte dye. Still images show control versus dynein shRNA islets reporting calcium activity after exposure to 11 mM glucose. Three representative regions of interest (ROIs) per islet are shown. Calbryte, red; cilia, green. Scale bar, 20 μm. Calcium response to glucose is delayed and dampened by ciliobrevin D, as shown by fluorescence intensity tracings and areas under the curve (AUCs). Traces are composite of three ROIs and representative of islets examined in three independent experiments. (B) Dynein knockdown in human islets results in reduced DNAI1 gene expression and diminished glucose-stimulated insulin secretion (GSIS); data are plotted from two independent knockdown experiments. Statistical significance was analyzed by Student’s t test and two-way ANOVA, *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001. (C) Gene set enrichment analysis (GSEA) of a published human RNA-seq study (47) showing differential expression of motile cilia genes in beta cells versus acinar cells. Red-blue color bar represents the gene order in beta cells (red, left) to acinar cells (blue, right). Each black line above the color bar represents a high-confidence ciliary gene in the reference gene set CiliaCarta (48). More black lines are enriched toward the left, showing greater frequency of ciliary gene detection in beta cells. (D) Increased expression of select motile cilia genes in human T2D beta cells. Z-transformed normalized average expression of ciliary genes in alpha and beta cells from healthy controls and patients with T2D. Source data from a published single-cell RNA-seq study (49).