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

Author

Listed:
  • Jantje M. Gerdes

    (The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet
    Institute for Diabetes and Regeneration Research, Helmholtz Center Munich, Business Campus Garching)

  • Sonia Christou-Savina

    (Molecular Medicine Unit, UCL Institute of Child Health)

  • Yan Xiong

    (The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet)

  • Tilo Moede

    (The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet)

  • Noah Moruzzi

    (The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet
    Institute for Diabetes and Regeneration Research, Helmholtz Center Munich, Business Campus Garching)

  • Patrick Karlsson-Edlund

    (The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet)

  • Barbara Leibiger

    (The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet)

  • Ingo B. Leibiger

    (The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet)

  • Claes-Göran Östenson

    (Endocrine and Diabetes Unit, Karolinska Institutet, Karolinska University Hospital)

  • Philip L. Beales

    (Molecular Medicine Unit, UCL Institute of Child Health)

  • Per-Olof Berggren

    (The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet)

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.

Suggested Citation

  • 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 Be, 2014. "Ciliary dysfunction impairs beta-cell insulin secretion and promotes development of type 2 diabetes in rodents," Nature Communications, Nature, vol. 5(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6308
    DOI: 10.1038/ncomms6308
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    Cited by:

    1. Andreas Müller & Nikolai Klena & Song Pang & Leticia Elizabeth Galicia Garcia & Oleksandra Topcheva & Solange Aurrecoechea Duran & Davud Sulaymankhil & Monika Seliskar & Hassan Mziaut & Eyke Schöniger, 2024. "Structure, interaction and nervous connectivity of beta cell primary cilia," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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