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 language | English |
|---|---|
| Article number | 6308 |
| Journal | Nature Communications |
| Volume | 5 |
| DOIs | |
| State | Published - 2014 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Chemistry(all)
- Physics and Astronomy(all)
Cite this
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 journal › Article
}
TY - JOUR
T1 - Ciliary dysfunction impairs beta-cell insulin secretion and promotes development of type 2 diabetes in rodents
AU - Gerdes, Jantje M.
AU - Christou-Savina, Sonia
AU - Xiong, Yan
AU - Moede, Tilo
AU - Moruzzi, Noah
AU - Karlsson-Edlund, Patrick
AU - Leibiger, Barbara
AU - Leibiger, Ingo B.
AU - Östenson, Claes Göran
AU - Beales, Philip L.
AU - Berggren, Per Olof
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84923277743&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84923277743&partnerID=8YFLogxK
U2 - 10.1038/ncomms6308
DO - 10.1038/ncomms6308
M3 - Article
AN - SCOPUS:84923277743
VL - 5
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 6308
ER -