Influences of exendin-4 on the secretion function of islet beta cells from rats in the early stage of severe scald

Objective To observe the secretion function changes of islet beta cells isolated from rats in the early stage of severe scald, and to explore the influence of them. Methods Thirty-six Wistar rats were divided into sham injury (SI) group, sham injury+ exendin-4 (SIE) group, scald (S) group, and scald+ exendin-4 (SE) group according to the random number table, with 9 rats in each group. Rats in groups S and SE were inflicted with 50% total body surface area full-thickness scald by a 12-s immersion of back and a 6-s immersion of abdomen in 94 ℃ hot water. Rats in groups SI and SIE were sham injured through immersion of back and abdomen in 37 ℃ warm water. Rats in groups S and SE were subcutaneously injected with exendin-4 (4 μg/kg) twice a day post injury, while rats in groups SI and SIE were subcutaneously injected with sterile water in the same volume. At post injury hour (PIH) 72, the following detections were performed. Eight rats of each group were respectively selected to measure level of fasting blood glucose with cutting-tail method, and to detect plasma level of glucagon-like peptide 1 (GLP-1) and serum level of insulin by enzyme-linked immunosorbent assay (ELISA). The insulin resistant index (HOMA-IR) was calculated. Six rats of each group were respectively selected for islet isolation. The isolated rat islets were stimulated with RPMI 1640 medium containing 2.8 or 16.7 mmol/L glucose, respectively. Insulin content in supernatant was detected by ELISA, and insulin secretion index was calculated with 6 samples in each group. The isolated islets from 3 rats of each group were selected for the observation of the super-structure of islet beta cells under transmission electron microscope. The number of docked granules in per 10 μm membrane of islet beta cells and the ratio of insulin vesicles to the total insulin granules were calculated with 3 samples in each group. Data were processed with one-way analysis of variance and LSD test. Results (1) Compared with that in group S, levels of fasting blood glucose of rats in group SI, SIE, and SE were significantly decreased (P<0.05 or P<0.01). (2) Compared with those in group SI, plasma level of GLP-1 of rats in group SIE was significantly increased (P<0.05), while serum level of insulin and HOMA-IR of rats did not change obviously (with P values above 0.05). Plasma levels of GLP-1 of rats in groups S and SE were significantly decreased (with P values below 0.01), while serum levels of insulin and HOMA-IR were obviously increased (with P values below 0.01). Compared with those in group SIE, plasma levels of GLP-1 of rats in groups S and SE were significantly decreased (with P values below 0.01), while serum levels of insulin and HOMA-IR were significantly increased (with P values below 0.01). Compared with those in group S, plasma level of GLP-1 and serum level of insulin of rats in group SE were significantly increased (with P values below 0.01), while HOMA-IR was significantly decreased (P<0.05). (3) There was no statistically significant difference in the insulin secretion content of rats in the 4 groups when stimulated with 2.8 mmol/L glucose (P>0.05). Under stimulation of 16.7 mmol/L glucose, compared with that in group SI, the insulin secretion content of rats in groups SIE and SE were significantly increased (P<0.05 or P<0.01), while in group S it was significantly decreased (P<0.05). Compared with that in group SE, the insulin secretion content of rats in group S was significantly decreased (P<0.01) . Compared with that in group S, the insulin secretion content of rats in group SE was significantly increased (P<0.01). Compared with that in group SI (2.25±0.20), the insulin secretion index of rats in group SE (2.68±0.24) was significantly increased (P<0.05). Compared with that in group SIE (2.47±0.18), the insulin secretion index of rats in group S (2.11±0.28) was significantly decreased (P<0.05). Compared with that in group S, the insulin secretion index of rats in group SE was significantly increased (P<0.01). (4) Compared with those in group SI, the number of docked granules per 10 μm membrane of islet beta cells in group SE was significantly increased (P<0.05), while the ratio of insulin vesicles of rat islet beta cells in group S was significantly increased (P<0.01). Compared with those in group SE, the number of docked granules per 10 μm membrane of islet beta cells in group S was significantly decreased (P<0.01), while the ratio of insulin vesicles of rat islet beta cells was significantly increased (P<0.05). Compared with those in group S, the number of docked granules per 10 μm membrane of islet beta cells in group SE was significantly increased (P<0.01), while the ratio of insulin vesicles of rat islet beta cells was significantly decreased (P<0.05). Conclusions In the early stage of severe scald in rats, level of GLP-1 is decreased and the insulin secretion function of islet beta cells is injured. Long-lasting GLP-1 analogous exendin-4 can improve the secretion function of isolated islet beta cells from severely scalded rats.