Effects of Exendin-4 on pancreatic islets function in treating hyperglycemia post severe scald injury in rats.

BACKGROUND:It has been established that glucagon-like peptide 1 (GLP 1) inhibits pancreatic β-cell apoptosis, increases insulin secretion, and improves glucose tolerance in scald injury. However, the effects of Exendin-4, a long-acting incretin similar to GLP 1, remained unclear in severe scald injury. Hence, this study attempted to investigate whether Exendin-4 had similar effects by protecting the histology of pancreas in severely scalded rats. METHODS:One hundred sixty-two adult Wistar rats were equally randomized to sham burn group, burn group and burn with Exendin-4 treatment group. Rats were subjected to full skin thickness scald injuries (total body surface area: 50%) and were injected subcutaneously with Exendin-4 (4 μg/kg) twice daily. The histological changes of islets, the apoptosis of β cells, the amount of glucagon and insulin, and the concentration of plasma glucagon and insulin were observed; and the intraperitoneal glucose tolerance test was performed as well. RESULTS:The islets and β cells were injured and the number of secretory granules decreased in the scalded rats, but less histopathological changes were seen in the rats treated with Exendin-4. The apoptosis index of treated rats was significantly lower than that of the scalded rats (p < 0.05). There was significant difference in β-cell density postinjury between the two groups (p < 0.05). More insulin and less glucagon in islets and plasma were found in the treated rats (p < 0.05), suggesting improved intraperitoneal glucose tolerance (p < 0.05) and fasting blood glucose (p < 0.05) in this group. CONCLUSION:Based on our previous finding that GLP-1 could control hyperglycemia by increasing insulin secretion and inhibiting β-cell apoptosis in severe scald injuries, this study further confirmed that Exendin-4 could increase glycemic control following severe scald by preserving the histology of β cells in pancreatic islets and inhibiting their apoptosis.