Betacellulin ameliorates hyperglycemia in obese diabetic db/db mice.

Betacellulin ameliorates hyperglycemia in obese diabetic db/db mice. J Mol Med (Berl). 2015 Jun 14; Authors: Oh YS, Shin S, Li HY, Park EY, Lee SM, Choi CS, Lim Y, Jung HS, Jun HS 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(2+) 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 ...
Source: Molecular Medicine - Category: Molecular Biology Authors: Tags: J Mol Med (Berl) Source Type: research