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Identification of four mouse diabetes candidate genes altering β-cell proliferation.
PLoS Genet. 11:e1005506 (2015)
Beta-cell apoptosis and failure to induce beta-cell regeneration are hallmarks of type 2-like diabetes in mouse models. Here we show that islets from obese, diabetes-susceptible New Zealand Obese (NZO) mice, in contrast to diabetes-resistant C57BL/6J (B6)-ob/ob mice, do not proliferate in response to an in-vivo glucose challenge but lose their beta-cells. Genome-wide RNAseq based transcriptomics indicated an induction of 22 cell cycle-associated genes in B6-ob/ob islets that did not respond in NZO islets. Of all genes differentially expressed in islets of the two strains, seven mapped to the diabesity QTL Nob3, and were hypomorphic in either NZO (Lefty1, Apoa2, Pcp4l1, Mndal, Slamf7, Pydc3) or B6 (Ifi202b). Adenoviral overexpression of Lefty1, Apoa2, and Pcp4l1 in primary islet cells increased proliferation, whereas overexpression of Ifi202b suppressed it. We conclude that the identified genes in synergy with obesity and insulin resistance participate in adaptive islet hyperplasia and prevention from severe diabetes in B6-ob/ob mice.
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Publication type
Article: Journal article
Document type
Scientific Article
ISSN (print) / ISBN
1553-7390
e-ISSN
1553-7404
Journal
PLoS Genetics
Quellenangaben
Volume: 11,
Issue: 9,
Article Number: e1005506
Publisher
Public Library of Science (PLoS)
Non-patent literature
Publications
Reviewing status
Peer reviewed