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

Research output: Contribution to journalArticle

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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

Fingerprint

rodents
insulin
secretions
Medical problems
Basal Bodies
Type 2 Diabetes Mellitus
Rodentia
Insulin
Ciliary Body
Cilia
cells
Islets of Langerhans
obesity
diabetes mellitus
Insulin Receptor
magnetic permeability
Gene expression
gene expression
Rats
glucose

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., ... 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

Ciliary dysfunction impairs beta-cell insulin secretion and promotes development of type 2 diabetes in rodents. / Gerdes, Jantje M.; Christou-Savina, Sonia; Xiong, Yan; Moede, Tilo; Moruzzi, Noah; Karlsson-Edlund, Patrick; Leibiger, Barbara; Leibiger, Ingo B.; Östenson, Claes Göran; Beales, Philip L.; Berggren, Per Olof.

In: Nature Communications, Vol. 5, 6308, 2014.

Research output: Contribution to journalArticle

Gerdes, JM, Christou-Savina, S, Xiong, Y, Moede, T, Moruzzi, N, Karlsson-Edlund, P, Leibiger, B, Leibiger, IB, Östenson, CG, Beales, PL & Berggren, PO 2014, 'Ciliary dysfunction impairs beta-cell insulin secretion and promotes development of type 2 diabetes in rodents', Nature Communications, vol. 5, 6308. https://doi.org/10.1038/ncomms6308
Gerdes, Jantje M. ; Christou-Savina, Sonia ; Xiong, Yan ; Moede, Tilo ; Moruzzi, Noah ; Karlsson-Edlund, Patrick ; Leibiger, Barbara ; Leibiger, Ingo B. ; Östenson, Claes Göran ; Beales, Philip L. ; Berggren, Per Olof. / Ciliary dysfunction impairs beta-cell insulin secretion and promotes development of type 2 diabetes in rodents. In: Nature Communications. 2014 ; Vol. 5.
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