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

• Applicant: Professor Dr. Rolf Michael Nüsing
• Subject Area: Pharmacology
• Term: from 2013 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 233991743

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.

• DFG Programme: Research Grants