, Volume 35, Issue 2, pp 723–729

Timing of Insulin Therapy Affects the Inflammatory Response in Endotoxemic Rats

  • Bo Zou
  • Qiyi Chen
  • Shaoqiu Tang
  • Tao Gao
  • Juanjuan Zhang
  • Fengchan Xi
  • Wenkui Yu


The aim of the present study was to determine whether timing of insulin administration influences the hepatic and serum proinflammatory and anti-inflammatory cytokines during endotoxemia stimulated by lipopolysaccharide (LPS). Eighty-one male Sprague–Dawley rats were divided into different time groups and insulin was given 30 min pre-LPS administration or hour 0, 1, 3, 6, 12, 24 after the induction of endotoxemia, respectively. Hepatic and serum proinflammatory cytokines IL-1β, IL-6, and TNF-α, and anti-inflammatory cytokine IL-10 were detected 24 and 48 h after the induction of endotoxemia. Compared with sham control rats, serum concentrations of proinflammatory cytokines IL-1β, IL-6, and TNF-α and anti-inflammatory cytokine IL-10 significantly increased on 24 and 48 h after induction of endotoxemia. Similarly, LPS administration also significantly increased the hepatic IL-1β, TNF-α, IL-6, and IL-10 protein concentration 48 h after LPS injection. Compared with levels in positive LPS controls animals receiving saline, on 24 and 48 h after LPS injection, insulin administrated ahead of 6 h after LPS injection significantly decreased the serum IL-1β, IL-6, and TNF-a concentration (P < 0.05), and significantly increased anti-inflammatory cytokine IL-10 concentration (P < 0.05); hepatic IL-1β and IL-6 expression were (P < 0.05) significantly decreased compared with levels in positive LPS controls. But, the significant decrease of hepatic TNF-a expression and significant increase of hepatic IL-10 were only seen in the animals in which insulin was administrated at 30 min pre-LPS or coadministrated with LPS. Insulin administrated 6 h after LPS injection lost the ability to significantly reduce serum or hepatic IL-1β, TNF-α, and IL-6 concentrations. Insulin has a protective role in systemic inflammatory response syndrome related to sepsis, such as downregulation of proinflammatory cytokines and upregulation of anti-inflammatory cytokine production. However, timing of insulin administrated may change its effect of inflammatory response in endotoxemic rats. Insulin administrated 6 h after LPS injection weaken the ability to protect inflammatory response related to sepsis.


insulin endotoxin proinflammatory cytokine anti-inflammatory cytokine timing of therapy 


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Bo Zou
    • 1
  • Qiyi Chen
    • 1
  • Shaoqiu Tang
    • 1
  • Tao Gao
    • 2
  • Juanjuan Zhang
    • 2
  • Fengchan Xi
    • 2
  • Wenkui Yu
    • 2
  1. 1.Medical School of Nanjing UniversityNanjingChina
  2. 2.Research Institute of General SurgeryNanjing General Hospital of Nanjing Military CommandNanjingChina

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