The PGD2 system, a new target to treat type 1 diabetes

1型糖尿病在大多数情况下被认为是由产生胰岛素的胰腺β细胞的自身免疫性破坏引起的。炎症和免疫调节作用的前列腺素类被认为参与其中，然而，它们的确切作用尚未解决。目前广泛建立的多次小剂量链脲佐菌素糖尿病模型与人类的病理情况非常相似。使用这种类型的模型，我们获得的初步数据表明，PGD 2受体的敲除或抑制引起诱导的高血糖症的抑制和胰腺功能的恢复。我们的结论是，PGD 2在糖尿病发病机制中起着重要的，但未知的，炎症/免疫调节作用，PGD 2拮抗剂可能代表一种新的治疗选择，以治疗/预防1型糖尿病。为了支持这一假设，我们的目标是：首先确定胰腺酶和PGD 2受体及其在糖尿病诱导过程中的调节;其次确定保护免受糖尿病所需的PGD 2拮抗作用的确切时间窗;第三确定潜在的抗糖尿病机制;第四在自身免疫NOD小鼠中验证我们在链脲佐菌素非依赖性糖尿病动物模型中的数据。

Type 1 diabetes is considered in most cases to result from an autoimmune destruction of the insulin-producing pancreatic beta cells. Inflammatory and immune modulatory acting prostanoids are suggested to be involved, however, their exact role is unsolved. The widely established muliple low dose streptozotocin model of diabetes exerts great similarity to the human pathological situation. Using this type of model we gained preliminary data showing that knockout or inhibition of the PGD2 receptor causes suppression of induced hyperglycemia and restoration of pancreatic function. We conclude that PGD2 plays an important, yet unknown, inflammatory/immune modulatory role in diabetes pathogenesis and that PGD2 antagonism may represent a novel therapeutic option to treat/prevent type 1 diabetes. To support this assumption our aims are: first to identify pancreatic enzymes and receptors of PGD2 and their regulation during induction of diabetes; second to identify the exact time window of PGD2 antagonism necessary to protect from diabetes; third to identify the underlying antidiabetogenic mechanism(s); and fourth to verify our data in a streptozotocin-independent animal model of diabetes, in the autoimmune NOD mouse.