| First Author | Dirice E | Year | 2019 |
| Journal | JCI Insight | Volume | 4 |
| Issue | 8 | PubMed ID | 30996131 |
| Mgi Jnum | J:291458 | Mgi Id | MGI:6443063 |
| Doi | 10.1172/jci.insight.99576 | Citation | Dirice E, et al. (2019) Human duct cells contribute to beta cell compensation in insulin resistance. JCI Insight 4(8) |
| abstractText | The identification of new sources of beta cells is an important endeavor with therapeutic implications for diabetes. Insulin resistance, in physiological states such as pregnancy or in pathological states such as type 2 diabetes (T2D), is characterized by a compensatory increase in beta cell mass. To explore the existence of a dynamic beta cell reserve, we superimposed pregnancy on the liver-specific insulin receptor-KO (LIRKO) model of insulin resistance that already exhibits beta cell hyperplasia and used lineage tracing to track the source of new beta cells. Although both control and LIRKO mice displayed increased beta cell mass in response to the relative insulin resistance of pregnancy, the further increase in mass in the latter supported a dynamic source that could be traced to pancreatic ducts. Two observations support the translational significance of these findings. First, NOD/SCID-gamma LIRKO mice that became pregnant following cotransplantation of human islets and human ducts under the kidney capsule showed enhanced beta cell proliferation and an increase in ductal cells positive for transcription factors expressed during beta cell development. Second, we identified duct cells positive for immature beta cell markers in pancreas sections from pregnant humans and in individuals with T2D. Taken together, during increased insulin demand, ductal cells contribute to the compensatory beta cell pool by differentiation/neogenesis. |
