The Effect Of Intensive Insulin Therapy On Stress Hyperglycaemia Of Rabbits With Sepsis And Its Mechanism

Objective The present study was performed to (1) investigate the effect of intensive insulin therapy on stress hyperglycemia of rabbits with sepsis;(2) clarify the changes in levels of GLUT4, proinflammatory cytokines and hormones during sepsis;and the effect of intensive insulin therapy on them;(3) elucidate the impact of intensive insulin therapy on glycometabolism, proteometabolism and inflammatory response in septic rabbits.Materials and Methods Septic rabbit model was made by standard cecal ligation and puncture (CLP). Ninty three rabbits were randomly divided into 3 groups: control group(sham operation group, n=17), CLP group(n=38) and intensive insulin therapy group(n=38). Control animals underwent anesthesia and laparotomy only. CLP group animals received operation of CLP. Therapy group animals received intensive insulin therapy immediately after CLP to control blood glucose strictly within normal range. All rabbits were banned on food and water after operation and received intravenous nutrition only. Blood samples were collected from internal jugular vein at designed time points till 72h. After centrifugation, blood samples were stored at -20 °C. Skeletal muscle of hind legs was collected in sterile tube and stored in liquid nitrogen. Blood glucose was monitored by fast blood sugar meter. GLUT4 mRNA level was analyzed by RT-PCR and its protein level was determined by Western-blotting method. TNF-a level was measured by ELISA. Blood insulin, cortisol and glucagon were measured by radioimmunoassay. Blood albumin was measured by auto-biochemical analyzer.Results (1) Blood sugar level in CLP group was much higher than that in control group. Blood sugar level in intensive insulin therapy group was in normal range. (2) GLUT4 mRNA expression in skeletal muscle of CLP group decreasedat 2h (p<0.05), reached the lowest at 12h (p<0.0l);its protein level also began to decrease at 2h (p<0.05), and reached the lowest at 24h (p<0.0l). Intensive insulin therapy could inhibit this decrease. (3) Compared with control group, TNF-a level in CLP group was much higher. TNF-a level in intensive insulin therapy group was higher than that of control group too, but markedly lower than that of CLP group. (4) The plasma level in insulin, cortisol and glucagon in CLP group began to increase at 2h after injury (p<0.05), reached it's peak at 12h (p<0.01). Intensive insulin therapy could markedly inhibit this increase. (5) Blood albumin level in CLP group decreased at 6h after injury (p<0.05), reached the lowest at 24h (p<0.01), intensive insulin therapy could inhibit the decrease dramatically. (6) Suvival rate (3 days) of intensive insulin therapy group (75%) was much higher than that of CLP group (41.6%,p<0.01).Conclusion Sepsis can cause stress hyperglycemia, decrease in GLUT4 mRNA and protein level, and increase in hormones and proinflammatory cytokines. Intensive insulin therapy can increase GLUT4 expression in skeletal muscle, control the stress hyperglycemia, and inhibit the excessive release of hormones and cytokines in septic animals. The experimental data indicate that intensive insulin therapy can give promising benefits to metabolism of sugar and protein, inhibit excessive inflammatory response, and improve the prognosis thereby.