Figure 7

Schematic showing the proposed role that IHoP has in the progression of type 1 diabetes. Healthy pancreatic islets are in cellular and hormonal homeostasis. An increase in IHoP expression disrupts the balance within an islet causing glucose levels to increase resulting in pre-onset disease. Without intervention, levels of glucagon and IHoP continue to increase, and type 1 diabetes develops resulting in islet destruction (lower pathway). However, if IHoP is suppressed at the pre-onset stage, homeostasis is restored and the islet is able to regenerate through activation of the PDX-1 pathway by Reg-3γ (upper pathway). The dashed blue line represents an arbitrary point in the progression of the disease, this point is something like a point of no return. Based on our data, we feel that if treatment is given before this point of no return the progression of the disease can be altered and the animals survive with normal glycemic levels, but if treatment is given after this point the disease progresses toward full onset of the T1D. Once the disease is considered full onset, the damage has been done and IHoP’s role is insufficient to rescue the islet.