Pathways that drive beta cell proliferation or expansion while retaining normal beta cell function could be exploited to expand and restore beta cell mass in individuals with type 1 diabetes. In order to understand the pathways regulating beta cell proliferation, these investigators examined the cell cycle regulatory process in a special group of rodent beta cells that have the ability to continuously and indefinitely proliferate. From this analysis, the researchers identified a single protein, called cMyc, responsible for the continuous beta cell proliferation. The team also demonstrated that a low level of cMyc is able to stimulate beta cell proliferation of normal human beta cells while maintaining normal beta cell function and without causing cell death. This work suggests that low-level activation of cMyc is a normal mechanism for stimulating beta cell proliferation and that drugs that regulate cMyc in a careful and physiologic manner could be attractive as targets to drive therapeutic human beta cell expansion.
Karslioglu, E., Kleinberger, JW., Salim, FG., Cox AE, Takane KK, Scott DK, Stewart AF. (2011). cMyc is a principal upstream driver of beta-cell proliferation in rat insulinoma cell lines and is an effective mediator of human beta-cell replication. Mol. Endocrinol. 25, 1760-1772.
Ramifications for Individuals with Type 1 Diabetes:
This early stage research demonstrates that low-level activation of cMyc can stimulate expansion of human beta cells while retaining normal function. While this suggests that cMyc might be a viable target for therapies to promote beta cell regeneration, it should be noted that side effects have been associated with this protein. Before any therapeutic potential could be realized, additional work will be required to further validate cMyc’s role in beta cell expansion and to identify safe, selective and regulated mechanisms to stimulate cMyc in the beta cell.
This work was supported in part by JDRF grants Dr. Stewart.