| First Author | Zhang M | Year | 2016 |
| Journal | Proc Natl Acad Sci U S A | Volume | 113 |
| Issue | 3 | Pages | 650-5 |
| PubMed ID | 26733677 | Mgi Jnum | J:229942 |
| Mgi Id | MGI:5754920 | Doi | 10.1073/pnas.1524200113 |
| Citation | Zhang M, et al. (2016) Growth factors and medium hyperglycemia induce Sox9+ ductal cell differentiation into beta cells in mice with reversal of diabetes. Proc Natl Acad Sci U S A 113(3):650-5 |
| abstractText | We previously reported that long-term administration of a low dose of gastrin and epidermal growth factor (GE) augments beta-cell neogenesis in late-stage diabetic autoimmune mice after eliminating insulitis by induction of mixed chimerism. However, the source of beta-cell neogenesis is still unknown. SRY (sex-determining region Y)-box 9(+) (Sox9(+)) ductal cells in the adult pancreas are clonogenic and can give rise to insulin-producing beta cells in an in vitro culture. Whether Sox9(+) ductal cells in the adult pancreas can give rise to beta cells in vivo remains controversial. Here, using lineage-tracing with genetic labeling of Insulin- or Sox9-expressing cells, we show that hyperglycemia (>300 mg/dL) is required for inducing Sox9(+) ductal cell differentiation into insulin-producing beta cells, and medium hyperglycemia (300-450 mg/dL) in combination with long-term administration of low-dose GE synergistically augments differentiation and is associated with normalization of blood glucose in nonautoimmune diabetic C57BL/6 mice. Short-term administration of high-dose GE cannot augment differentiation, although it can augment preexisting beta-cell replication. These results indicate that medium hyperglycemia combined with long-term administration of low-dose GE represents one way to induce Sox9(+) ductal cell differentiation into beta cells in adult mice. |
