@article{be22f051104b4270a881c43b1f459f07,
title = "Ciliary dysfunction impairs beta-cell insulin secretion and promotes development of type 2 diabetes in rodents",
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.",
author = "Gerdes, {Jantje M.} and Sonia Christou-Savina and Yan Xiong and Tilo Moede and Noah Moruzzi and Patrick Karlsson-Edlund and Barbara Leibiger and Leibiger, {Ingo B.} and {\"O}stenson, {Claes G{\"o}ran} and Beales, {Philip L.} and Berggren, {Per Olof}",
note = "Funding Information: We thank Elisabeth Nor{\'e}n-Krog, Elisabetta Dar{\'e}, Lisa Juntti-Berggren, Lars Selander, Alan Bahow, Gustavo de Abreu-Vieira, Hannelore Rother, Christopher Illies, as well as other members of the Berggren laboratory for their collegiality and helpful discussions. This work was supported by a Marie Curie International Re-Integration Grant (PIRG07-GA-2010-268397) and funds from F{\"o}reningen fr{\"a}mj{\"o}rande Diabetes Forskning (FFDF) and KI stiftelse to J.M.G., by funds from Karolinska Institutet and by grants from the Swedish Research Council, the Novo Nordisk Foundation, the Swedish Diabetes Association, the Family Knut and Alice Wallenberg Foundation, Diabetes Research and Wellness Foundation, Berth von Kantzow{\textquoteright}s Foundation, the Skandia Insurance Company, Ltd, the Strategic Research Programme in Diabetes at Karolinska Institutet, ERC-2013-AdG 338936-BetaImage, the Stichting af Jochnick Foundation and the Family Erling-Persson Foundation. Publisher Copyright: {\textcopyright} 2014 Macmillan Publishers Limited. All rights reserved.",
year = "2014",
doi = "10.1038/ncomms6308",
language = "English (US)",
volume = "5",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}