405 The Glucagon-like Peptide-1 Analogue Exendin-4 Inhibiting Pancreatic Beta Cells Apoptosis, Increasing Insulin Secretion and Improving Glucose Tolerance in Severely Scalded Rat

Hyperglycemia is a universal and feared systemic response of patient underwent severe burn, which is associated with worse clinical outcomes and increase complications such as bacteremia, fungemia, reduced skin graft take, etc. The insulin therapy is still the gold standard to treat hyperglycemia after severe burn injury. However, several studies showed insulin therapy was related to a potential risk of life-threatening hypoglycaemia, which offsets the beneficial effects of insulin. Several studies demonstrated that glucagon-like peptide-1 (GLP-1) could prevent pancreatic β cell from apoptosis and increase glucose-stimulated insulin secretion. Exendin-4, a glucagon-like peptide-1 receptor agonist has been demonstrated to have a greater biological half-life than GLP-1 and it may have more potent than GLP-1 use in treating type 2 diabetes. However, the effectiveness of exendin-4 in severe burn is still unclear. The aim of the present study was to investigate whether exendin-4 could inhibit pancreatic β cell apoptosis and improve glycaemia in severely scalded rat. Adult male Wistar rats were randomly divided into three groups: sham burn group, scalded burn group and scalded burn with exendin-4 treatment group. The pancreatic β cell apoptosis was assayed by TUNEL staining. The pancreatic tissues were harvested to evaluate glucagon and insulin expression using double immunofluorescence staining; and the intraperitoneal glucose tolerance test was performed to evaluate the glucose tolerance. We found the morphology of pancreatic β cell in exendin-4 treatment group with clear boundary and more regular than scalded burn group at 1, 3 or 5 days post-burn injury. Compared with scalded burn group, we found exendin-4 treatment significantly (F=231.250, P<0.001) inhibited the apoptosis of pancreatic β cell after treating day 1 (22.23 ± 4.04 vs 27.81 ± 4.57, P<0.001), day3 (18.60 ± 3.89 vs 36.26 ± 5.43, P<0.00) and day 5 (15.08 ± 4.26 vs 30.53 ± 3.89, P<0.001), respectively. Furthermore, the exendin-4 treatment also significantly increased insulin secretion (F=772.105, P<0.001) and improving glucose tolerance after burn injury(F=70.435, P<0.001). The present study provide evidence that exendin-4 could protect pancreatic β cell from apoptosis, increase insulin secretion and improve glucose tolerance after severely scalded burn injury. The experiment data can provide the theoretical possibility of using Exendin-4 in the treatment of hyperglycemia following burn injuryin humans.