期刊
JOURNAL OF DIABETES RESEARCH
卷 2016, 期 -, 页码 -出版社
HINDAWI LTD
DOI: 10.1155/2016/3459246
关键词
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资金
- Yamagata University [35]
- JSPS KAKENHI [16790142, 18790168, 21590429, 24590473, 15K08417]
- Joint Research Program of Joint Usage/Research Center at the Institute of Development, Aging and Cancer (IDAC), Tohoku University [30 [2013], 6 [2014], 3 [2015]]
- Grants-in-Aid for Scientific Research [21590429, 16790142, 18790168, 15K08417, 24590473] Funding Source: KAKEN
Cryptochrome proteins (CRYs), which can bind noncovalently to cofactor (chromophore) flavin adenine dinucleotide (FAD), occur widely among organisms. CRYs play indispensable roles in the generation of circadian rhythm in mammals. Transgenic mice (Tg mice), ubiquitously expressing mouse CRY1 having a mutation in which cysteine414 (the zinc-binding site of CRY1) being replaced with alanine, display unique phenotypes in their circadian rhythms. Moreover, male Tg mice exhibit symptoms of diabetes characterized by beta-cell dysfunction, resembling human maturity onset diabetes of the young (MODY). The lowered proliferation of beta-cells is a primary cause of age-dependent beta-cell loss. Furthermore, unusually enlarged duct-like structures developed prominently in the Tg mice pancreases. The duct-like structures contained insulin-positive cells, suggesting neogenesis ;of beta-cells in the Tg mice. This review, based mainly on the author's investigation of the unique features of Tg mice, presents reported results and recent findings related to molecular processes associated with mammalian cryptochromes, especially their involvement in the regulation of metabolism. New information is described with emphasis on the aspects of islet architecture, pancreatic beta-cell dysfunction, and regeneration.
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