Osteoprotegerin promotes islet ? cell proliferation in intrauterine growth retardation rats through the PI3K/AKT/FoxO1 pathway.

ABSTRACT: Osteoprotegerin (OPG) is a critical factor involved in bone metabolism. The level of OPG is increased in the serum of diabetic patients; however, there is no consensus in prior studies on the role of OPG in regulating the function of islet ? cells. A rat model of intrauterine growth retardation (IUGR) was established in the present study to investigate whether OPG could enhance the proliferation of ? cells; and an in vitro culture model of rat islet ? cell line INS-1 was used, to confirm the effect of OPG supplementation and reveal the possible mechanism. The results showed that endogenous OPG expression was reduced and normal proliferation of ? cells was impaired in the IUGR islets. Exogenous supplement of OPG restored ? cell proliferation to an extent in the IUGR rats, possibly associated with regulation of the PI3K/AKT/FoxO1 signalling, as evidenced by the changes of protein expression in the pathway. Furthermore, treating rat islet INS-1 cells with a PI3K inhibitor, LY294002, blunted the effects of OPG supplement in promoting cell cycle and suppressing cell apoptosis. Taken together, the present work demonstrated that OPG supplementation could improve the proliferation of islet ? cells in IUGR, and the PI3K/AKT/FoxO1 pathway is involved in the underlying mechanism.

SUBMITTER: Tang S 

PROVIDER: S-EPMC6949609 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature