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

Abstract

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.

Hyperbaric oxygen treatment improves pancreatic β‑cell function and hepatic gluconeogenesis in STZ‑induced type‑2 diabetes mellitus model mice

“…The liver is an essential organ in glucose metabolism ( 38 ). Our previous study demonstrated that HBOT enhanced hepatic glycogen storage in T2DM mice ( 19 ). The results of the present study suggested that HBO improved the structure of hepatocytes and increased hepatic glycogen storage in T2DM mice.…”

“…Skeletal muscle serves an essential role in regulating blood glucose, accounting for ~75% of total glucose clearance ( 37 ). In type-1 diabetes mellitus (T1DM) model mice, HBOT improved glucose metabolism by protecting islet β-cells and enhancing hepatic glycogen storage ( 19 ).…”

“…Subsequently, the mice were sacrificed by exsanguination following an intraperitoneal injection of 50 mg/kg sodium pentobarbital. Blood samples were obtained from the orbital sinus and stored at −20°C or −80°C until further use ( 18 , 19 ).…”

Hyperbaric oxygen therapy affects insulin sensitivity/resistance by increasing adiponectin, resistin, and plasminogen activator inhibitor-I in rats

“…Both clinical and animal studies suggest that HBOT regulates blood glucose via many signaling pathways or molecules and leads to insulin sensitivity [30][31][32][33][34][35]. In the mouse study of type 1 DM conducted by Limin et al, it was suggested that with HBOT, more glycogen was stored in the liver, the ratio of the islet beta-cell area to the total islet area increased, the plasma total ghrelin level increased, and the glucose metabolism dysfunction was ameliorated [30].…”

Wip1 regulates the immunomodulatory effects of murine mesenchymal stem cells in type 1 diabetes mellitus via targeting IFN-α/BST2

“…To induce the T1DM model as previously described [ 38 , 39 ], male C57BL/6j mice were fed ad libitum for 48 h followed by food and water deprivation for 10–16 h before T1DM induction. Subsequently, streptozotocin (STZ, 50 mg/kg, Sigma-Aldrich, v900890) dissolved in sodium citrate buffer was administrated by intraperitoneal injection in the lower left abdomen once per day for 5 days.…”