Ciliary dysfunction impairs beta-cell insulin secretion and promotes development of type 2 diabetes in rodents

Jantje M. Gerdes, Sonia Christou-Savina, Yan Xiong, Tilo Moede, Noah Moruzzi, Patrick Karlsson-Edlund, Barbara Leibiger, Ingo B. Leibiger, Claes Göran Östenson, Philip L. Beales, Per Olof Berggren

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Abstract

Type 2 diabetes mellitus is affecting more than 382 million people worldwide. Although much progress has been made, a comprehensive understanding of the underlying disease mechanism is still lacking. Here we report a role for the β-cell primary cilium in type 2 diabetes susceptibility. We find impaired glucose handling in young Bbs4-/- mice before the onset of obesity. Basal body/ciliary perturbation in murine pancreatic islets leads to impaired first phase insulin release ex and in vivo. Insulin receptor is recruited to the cilium of stimulated β-cells and ciliary/basal body integrity is required for activation of downstream targets of insulin signalling. We also observe a reduction in the number of ciliated β-cells along with misregulated ciliary/basal body gene expression in pancreatic islets in a diabetic rat model. We suggest that ciliary function is implicated in insulin secretion and insulin signalling in the β-cell and that ciliary dysfunction could contribute to type 2 diabetes susceptibility.

Original languageEnglish
Article number6308
JournalNature Communications
Volume5
DOIs
StatePublished - 2014
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Gerdes, J. M., Christou-Savina, S., Xiong, Y., Moede, T., Moruzzi, N., Karlsson-Edlund, P., Leibiger, B., Leibiger, I. B., Östenson, C. G., Beales, P. L., & Berggren, P. O. (2014). Ciliary dysfunction impairs beta-cell insulin secretion and promotes development of type 2 diabetes in rodents. Nature Communications, 5, [6308]. https://doi.org/10.1038/ncomms6308