Blocking Ghrelin Receptor Improves Pancreatic Islet Transplant Success

Islet transplantation offers a promising treatment for Type 1 Diabetes by restoring insulin production, but its widespread success is hampered by poor graft survival and function due to inflammation and immune rejection. The hormone ghrelin, known for regulating appetite and metabolism, also plays a role in pancreatic islet function and survival. This study addresses the critical knowledge gap of whether modulating ghrelin signaling can improve the outcomes of islet transplantation.

Treatment with the GHS-R1a antagonist significantly improved islet graft survival and function. The antagonist group demonstrated a remarkable 75% graft survival rate at 28 days, compared to only 30% in the vehicle-treated control group, indicating a 2.5-fold increase in successful engraftment. Fasting blood glucose levels in the treated mice were significantly lower, showing a 60% reduction compared to controls (p<0.001), returning to near-normal levels by day 14. > The most important finding was that blocking the ghrelin receptor GHS-R1a led to a substantial increase in islet graft survival and function, effectively reversing diabetes in a majority of treated animals. Histological analysis revealed better preserved islet morphology and higher insulin content in the grafts of antagonist-treated mice, suggesting enhanced beta-cell viability and function. Furthermore, the antagonist group exhibited a 2-fold increase in circulating insulin levels compared to controls (p<0.01), correlating with improved glucose homeostasis.