Modulation of Beta-Cell Intrinsic and Extrinsic Characteristics by CTGF to Promote Beta-Cell Mass Regeneration.

Abstract

As diabetes continues to affect millions of people within the United States, identification of novel factors that may enhance beta-cell proliferation and mass regeneration in vivo is critical. Our lab previously demonstrated the requirement of the secreted protein CTGF in endocrine development, specifically beta-cell differentiation and proliferation. However, over-expression of CTGF in normal adult beta-cells does not elicit beta-cell proliferation. Yet, CTGF is re-expressed in adult beta-cells during periods of beta-cell mass expansion, such as pregnancy and high fat diet feeding. Overall, this suggests that CTGF is critical during periods of increased beta-cell demand and beta-cell mass expansion, potentially including beta-cell regeneration. Through genetic mouse models we determined that CTGF over-expression promotes beta-cell regeneration via modulation of beta-cell maturity and proliferation characteristics. This is in addition to CTGF-mediated involvement of the immune system to promote beta-cell regeneration.