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.