Cell-based therapy is promising strategy for the cure of insulin deficient diabetes. One of such strategies, islet transplantation, has achieved remarkable success over the past decade, but its use is limited due to islet supply and graft survival. Another cell-based strategy is to regenerate the insulin-producing ?-cells from other cell types. In the preliminary studies, we explored a strategy to regenerate ?-cells from the neighboring glucagon-producing ?-cells in pancreatic islets. Specifically, we explored Pax4, a transcription factor critical for the determination of ?- vs ?-cell lineage during development, for this purpose. Our data showed Pax4 gene transfer into ?TC1.9 cells, a clonal ?-cell line, induced them to adopt ?-cell phenotype. We also found Pax4 gene transfer into primary human islets significantly improved ?-cell function, and had circumstantial evidence indicating Pax4 not only promoted ?-cell survival, but also induced ?-to-? cell conversion. Despite the extensive preliminary studies, more investigations are required in order to fully realize the therapeutic potential of Pax4 and to thoroughly understand its actions. We thus propose two specific aims in this project: 1) To investigate whether Pax4 gene transfer into donor human islets improves the therapeutic efficacy of islet transplantation; and 2) To investigate whether Pax4 induces ?-to-? cell conversion in primary islets and in vivo using lineage-tracing technology. Clearly, the project will provide important information regarding the therapeutic actions and potential of Pax4 for diabetes treatment.
| Kim, Do-Sung; Song, Lili; Wang, Jingjing et al. (2018) GRP94 Is an Essential Regulator of Pancreatic ?-Cell Development, Mass, and Function in Male Mice. Endocrinology 159:1062-1073 |
| Dong, Shengli; Wu, Hongju (2018) Regenerating ? cells of the pancreas - potential developments in diabetes treatment. Expert Opin Biol Ther 18:175-185 |
| Kim, Do-Sung; Song, Lili; Wang, Jingjing et al. (2018) Carbon Monoxide Inhibits Islet Apoptosis via Induction of Autophagy. Antioxid Redox Signal 28:1309-1322 |
| Dong, H; Zhang, Y; Wang, J et al. (2017) Regulator of G protein signaling 2 is a key regulator of pancreatic ?-cell mass and function. Cell Death Dis 8:e2821 |
| Zhang, Yanqing; Wu, Meifen; Htun, Wynn et al. (2017) Differential Effects of Linagliptin on the Function of Human Islets Isolated from Non-diabetic and Diabetic Donors. Sci Rep 7:7964 |
| Zhang, Yanqing; Fava, Genevieve E; Wu, Meifen et al. (2017) Effects of Linagliptin on Pancreatic ? Cells of Type 1 Diabetic Mice. J Endocr Soc 1:1224-1234 |
