The role of cilia genes in pancreatic beta-cell proliferation

Background and aims:

Type 2 diabetes (T2D) is determined by a complex interplay of genetics and environmental causes and is characterized by beta-cell apoptosis and the inability of adaptive beta-cell division. Recently, a focus was put on the role of primary cilia on beta-cell function. It was reported that cilia can affect insulin secretion. Here, we evaluated beta-cell ciliation and expression of cilia-annotated genes in pancreatic islets of two mouse strains that differ in diabetes-susceptibility as well as from diabetic and non-diabetic human donors.

Methods:

Obese diabetes-prone New Zealand Obese (NZO) and obese diabetes-resistant B6-ob/ob were fed a carbohydrate-free diet for 15 weeks and further challenged with a 2-day diabetogenic carbohydrate feeding. Ciliation of islets and regulation of cilia-genes were analyzed via immunohistochemistry and DNA-microarray, respectively. Resulting gene expression patterns were compared to human data.

Results:

NZO islets exhibit a lower number of cilia in comparison to B6-ob/ob islets. The cilia of B6-ob/ob mice disassembled in response to carbohydrate feeding. Transcriptome analysis identified 327 differently expressed cilia genes (DEG) of which 81 were also affected in human islets. Cilia genes high abundant in healthy subjects revealed an enrichment of genes involved in proliferation based on gen-ontology analysis.

Conclusion:

Our data provides evidence for the significant role of cilia and cilia-genes in the regulation of beta-cell proliferation in mice and men.