Reveresal of Diabetes by Pdx1-VP16 and Pax4-Induced Islet Regeneration

Pdx 1-VP 16和Pax 4诱导胰岛再生对糖尿病的治疗作用 已经证明内分泌胰腺具有再生的潜力，并且该过程可以 受Exendin-4等多种因素的影响。内源性β细胞再生的诱导可以 彻底改变糖尿病治疗尽管如此，还没有确定稳健的再生诱导方案 迄今已经证明关键的胰腺转录因子如Pdx 1和Pax 4可以重编程 干细胞有利于胰腺内分泌分化。了解所涉及的因素和机制 NFI细胞再生将指导治疗努力以增加糖尿病患者的FI细胞质量。 因此，我们假设胰腺转录因子的体内递送（即，Pdx 1-VP 16和Pax 4） nto糖尿病小鼠和非人灵长类动物的胰腺将促进胰岛细胞再生和恢复 胰腺内分泌功能 在这项研究中，我们将通过以下方法开辟再生途径： 1.确定Pdx 1-VP 16和Pax 4递送对血糖水平和胰岛细胞的影响， 在糖尿病小鼠模型中的再生。 2.为了确定Pdx 1-VP 16和Pax 4在促进胰岛细胞再生中的作用， 在有和没有自身免疫控制的情况下自发糖尿病NOD小鼠模型。 3.为了检测通过AAV 8载体将人Pdx 1递送至非人灵长类动物的胰腺是否 (NHP)患有自发性T2 DM可以逆转高血糖。 新的治疗策略可能来自于利用胰腺转录因子， 创新的方法来再生因糖尿病而失去的胰岛。

Reversal of Diabetes by Pdx1-VP16 and Pax4 Induced Islet Regeneration It has been demonstrated that endocrine pancreas has a potential to regeneration and the process could be facilitated by many factors like Exendin-4. The induction of endogenous beta cell regeneration could revolutionize diabetes therapy. Nonetheless, no robust regeneration-inducing protocol has been determined so far. Key pancreatic transcription factors such as Pdx1 and Pax4 has been demonstrated to reprogram stem cell in favor of endocrine pancreas differentiation. Understanding the factors and mechanisms involved n fi-cell regeneration will guide therapeutic efforts to augment fi-cell mass in patients with diabetes. Therefore, we hypothesize that in vivo delivery of pancreatic transcription factors (i.e., Pdx1-VP16 and Pax4) nto the pancreas of diabetic mice and nonhuman primates will promote islet cell regeneration and restore oancreatic endocrine function. In this study, we will blaze the trail to regeneration through the following approach: 1. To determine the effect of Pdx1-VP16 and Pax4 delivery on blood glucose levels and islet cell regeneration in a diabetic mouse model. 2. To determine the effects of Pdx1-VP16 and Pax4 on promoting islet cell regeneration in a spontaneous diabetic NOD mouse model in settings with and without control of autoimmunity. 3. To examine whether delivery of human Pdx1 by AAV8 vector to the pancreas of non-human primates (NHP) suffering from spontaneous T2DM can reverse hyperglycemia. It is possible that new therapeutic strategies may arise from harnessing pancreatic transcription factors in innovative ways in order to regenerate islets lost to diabetes.