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 and Per-Olof Berggren
Additional contact information
Jantje M. Gerdes: The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet
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
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

Nature Communications, 2014, vol. 5, issue 1, 1-13

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms6308

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