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ID 116748
Title Alternative
aPKC and DOC2b in glucose transport
Author
Nomiyama, Ryuta Yamaguchi University
Emoto, Masahiro Yamaguchi University|Emoto Clinic
Fukuda, Naofumi Yamaguchi University
Matsui, Kumiko Yamaguchi University
Kondo, Manabu Yamaguchi University
Tanizawa, Yukio Yamaguchi University
Keywords
Calcium sensor
Glucose transporter 4
Insulin signal
Content Type
Journal Article
Description
Aims/introduction: Double C2 domain protein b (DOC2b), one of the synaptotagmins, has been shown to translocate to the plasma membrane, and to initiate membrane-fusion processes of vesicles containing glucose transporter 4 proteins on insulin stimulation. However, the mechanism by which DOC2b is regulated remains unclear. Herein, we identified the upstream regulatory factors of DOC2b in insulin signal transduction. We also examined the role of DOC2b on systemic homeostasis using DOC2b knockout (KO) mice.
Materials and Methods: We first identified DOC2b binding proteins by immunoprecipitation and mutagenesis experiments. Then, DOC2b KO mice were generated by disrupting the first exon of the DOC2b gene. In addition to the histological examination, glucose metabolism was assessed by measuring parameters on glucose/insulin tolerance tests. Insulin-stimulated glucose uptake was also measured using isolated soleus muscle and epididymal adipose tissue.
Results: We identified an isoform of atypical protein kinase C (protein kinase C iota) that can bind to DOC2b and phosphorylates one of the serine residues of DOC2b (S34). This phosphorylation is essential for DOC2b translocation. DOC2b KO mice showed insulin resistance and impaired oral glucose tolerance on insulin and glucose tolerance tests, respectively. Insulin-stimulated glucose uptake was impaired in isolated soleus muscle and epididymal adipose tissues from DOC2b KO mice.
Conclusions: We propose a novel insulin signaling mechanism by which protein kinase C iota phosphorylates DOC2b, leading to glucose transporter 4 vesicle translocation, fusion and facilitation of glucose uptake in response to insulin. The present results also showed DOC2b to play important roles in systemic glucose homeostasis.
Journal Title
Journal of Diabetes Investigation
ISSN
20401124
NCID
AA12488319
Publisher
Asian Association for the Study of Diabetes|John Wiley & Sons
Volume
10
Issue
3
Start Page
591
End Page
601
Published Date
2018-10-27
Rights
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
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DOI (Published Version)
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language
eng
TextVersion
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departments
Medical Sciences