Octreotide Reduces Pancreatic Islet Apoptosis and Improves Islet Transplantation Efficiency In Vitro and In Vivo

The drug octreotide, a somatostatin analog, stimulates the cellular free radical scavenging system and inhibits the release of superoxide anions from monocytes. We hypothesized that octreotide also protects islet cell function and improves the survival of transplanted islets by ameliorating the adverse effects of hypoxia and reoxygenation on these cells, thus inhibiting apoptosis. To test this hypothesis, we experimentally induced hypoxia in islet beta cells in mouse insulinoma Min6 cells. Octreotide treatment mildly but significantly improved cell viability under normoxic and hypoxic conditions. Secreted vascular endothelial growth factor (VEGF) from the Min6 cells was downregulated after octreotide treatment during hypoxia. By contrast, the expression of hypoxia-inducible factor (HIF)-1 alpha was upregulated after octreotide treatment under both normoxic and hypoxic conditions. Octreotide treatment also lowered the apoptotic rate of Min6 cells under hypoxic conditions in vitro. In a mouse transplant model, octreotide improved the post-transplantation efficacy and function IP: 111 93 115 186 On: Wed 16 Dec 2020 05:29:06 of islet grafts. Expression of p53 and Bax in islegrafts was upregulated in the recipients treated with octreotide one day Copyright American Scientific Publishers after islet transplantation, and the octreotide-treated group produced significantly less Bax than the control group on days Delivered by Ingenta 3 and 7 following transplantation. TUNEL assay further demonstrated a decrease in islet cell apoptosis in the octreotide group on days 1, 3, 7, and 14 after transplantation compared with that of the control group (P < 0.05). No islet cell proliferation was found in the octreotide and control groups on days 1, 3, and 7 following transplantation. However, by day 14, the group treated with octreotide demonstrated significantly higher average cell proliferation rates than the controls did (P < 0.05). Thus, octreotide decreased the apoptosis of islets under hypoxic conditions in vitro and enhanced the efficacy of islet transplantation in vivo. Octreotide has excellent potential for therapeutic applications in islet transplantation and merits further study.