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- Title
Betacellulin ameliorates hyperglycemia in obese diabetic db/db mice.
- Authors
Oh, Yoon; Shin, Seungjin; Li, Hui; Park, Eun-Young; Lee, Song; Choi, Cheol; Lim, Yong; Jung, Hye; Jun, Hee-Sook
- Abstract
We found that administration of a recombinant adenovirus (rAd) expressing betacellulin (BTC) into obese diabetic db/db mice ameliorated hyperglycemia. Exogenous glucose clearance was significantly improved, and serum insulin levels were significantly higher in rAd-BTC-treated mice than rAd-β-gal-treated control mice. rAd-BTC treatment increased insulin/bromodeoxyuridine double-positive cells in the islets, and islets from rAd-BTC-treated mice exhibited a significant increase in the level of G1-S phase-related cyclins as compared with control mice. In addition, BTC treatment increased messenger RNA (mRNA) and protein levels of these cyclins and cyclin-dependent kinases in MIN-6 cells. BTC treatment induced intracellular Ca levels through phospholipase C-γ1 activation, and upregulated calcineurin B (CnB1) levels as well as calcineurin activity. Upregulation of CnB1 by BTC treatment was observed in isolated islet cells from db/db mice. When treated with CnB1 small interfering RNA (siRNA) in MIN-6 cells and isolated islets, induction of cell cycle regulators by BTC treatment was blocked and consequently reduced BTC-induced cell viability. As well as BTC's effects on cell survival and insulin secretion, our findings demonstrate a novel pathway by which BTC controls beta-cell regeneration in the obese diabetic condition by regulating G1-S phase cell cycle expression through Ca signaling pathways. Key messages:
- Subjects
HYPERGLYCEMIA treatment; OBESITY complications; ADENOVIRUSES; RECOMBINANT viruses; PROTEIN expression; SERUM; BROMODEOXYURIDINE; LABORATORY mice
- Publication
Journal of Molecular Medicine, 2015, Vol 93, Issue 11, p1235
- ISSN
0946-2716
- Publication type
Article
- DOI
10.1007/s00109-015-1303-1