Ghrelin system is involved in improvements in glucose metabolism mediated by hyperbaric oxygen treatment in a streptozotocin-induced type 1 diabetes mouse model

Type 1 diabetes mellitus (T1DM) is an autoimmune disorder for which the only effective therapy is insulin replacement. Hyperbaric oxygen (HBO) therapy has demonstrated potential in improving hyperglycemia and as a treatment option for T1DM. Ghrelin and HBO have been previously reported to exert proliferative, anti-apoptotic and anti-inflammatory effects in pancreatic cells. The present study investigated the mechanism underlying HBO- and ghrelin system-mediated regulation of glucose metabolism. Male C57BL/6 mice were intraperitoneally injected with streptozotocin (STZ; 150 mg/kg) to induce T1DM before the diabetic mice were randomly assigned into the T1DM and T1DM + HBO groups. Mice in the T1DM + HBO group received HBO (1 h; 100% oxygen; 2 atmospheres absolute) daily for 2 weeks. Significantly lower blood glucose levels and food intake were observed in mice in the T1DM + HBO group. Following HBO treatment, islet β-cell area were increased whereas those of α-cell were decreased in the pancreas. In addition, greater hepatic glycogen storage in liver was observed, which coincided with higher pancreatic glucose transporter 2 (GLUT2) expression levels and reduced hepatic GLUT2 membrane trafficking. There were also substantially higher total plasma ghrelin concentrations and gastric ghrelin-O-acyl transferase (GOAT) expression levels in mice in the T1DM + HBO group. HBO treatment also abolished reductions in pancreatic GOAT expression levels in T1DM mice. Additionally, hepatic growth hormone secretagogue receptor-1a levels were found to be lower in mice in the T1DM + HBO group compared with those in the T1DM group. These results suggest that HBO administration improved glucose metabolism in a STZ-induced T1DM mouse model. The underlying mechanism involves improved insulin-release, glucose-sensing and regulation of hepatic glycogen storage, an observation that was also likely dependent on the ghrelin signalling system.