Comparable findings had been also observed in the Pdx 1Cre.survivinlox lox mouse model, In other connected function, transplantation of pancreatic b cells engineered to ectopically express survivin from a rat insulin promoter into streptozotocin treated mice resulted in long term correction of hypergly cemia and rescue of streptozotocin induced b cell death, Together, these data propose that survivin is impor tant in the two the ordinary expansion within the b cell mass immediately after birth and in the survival of b cells following stress induced apoptosis. As both EGF and survivin are very important for b cell pro liferation, and as survivin expression is regulated by EGF in cancer cells, we hypothesized that EGF also reg ulates survivin expression in b cells and thereby is amongst the mechanisms involved in promoting b cell growth.
We chose the effectively established insulin producing b cell lines, MIN6 and INS 1, as an experimental model sys tem to test this hypothesis. Right here, we show that survivin is regulated by a number of inhibitor Epigenetic inhibitor pancreatic b cell development variables, such as glucose, insulin, and EGF. Induction of survi vin by EGF happens exceptionally quickly, inside of Temsirolimus mTOR inhibitor 15 minutes of treatment. The mechanism of EGF induced survivin takes place generally by means of activation from the ERK pathway and prolongation of survivin half life by inhibiting ubi quitin conjugation on the survivin protein. Hence, we’ve recognized a novel mechanism for survivin regula tion in pancreatic b cells that implicates ERK as a criti cal molecule for its publish translational modification and signaling for protein degradation.
Effects EGF regulates survivin protein expression in pancreatic b cells To start to comprehend the mitogenic responsiveness of survivin in pancreatic b cells we manufactured use of the immorta lized mouse and rat b cell lines, MIN6 and INS one. MIN6 cells have been cultured underneath proliferating conditions then serum and glucose deprived for two to four hrs, prior to remedy for thirty minutes with glucose or insulin. Success showed that various concentrations of glucose or insulin added for the cells can induce survivin protein expression at these early time points. MIN6 cells handled with glucose had a 10 fold improve in survivin protein levels at a concentration of 5.