The Relationship Between Nitric Oxide, Some Inflammatory Factors And Glucose Metabolism In Rats Of Peritoneal Infection

Background and aim: Insulin resistance (IR) is a common phenomenon in the clinical procedure. It has been proved that IR will result to the disturbance of metabolism of glucose, fat and protein. Van den Berghe point out that the mortality can be cut down through intensive insulin treatment to normalize blood glucose. Large amount of researches have been demonstrated that IR is associated with a state of acute inflammation, and several mediators released from various cell types, including immune cells and adipocytes, have been identified as being involved in the development of IR. Among those are several pro-inflammatory cytokines such as tumor necrosis factor-α(TNF-α) and interleukin(IL)-6. These inflammation factors play a central role in insulin resistance. Several, possibly cumulative, mechanisms by which TNF-αand IL-6 may impair insulin signaling have been proposed. Another mediator overproduced in sepsis is nitric oxide (NO), and NO is known to influence glucose metabolism by modulating the secretion of insulin and other pancreatic hormones. The secretion of NO can be regulated by administration of the L-arginine analog and NNLA, a competitive NOS inhibitor. Many experiments have been made on the correlation factors which influence the blood glucose level, but fewer studies concern about the effect of IL-6 and NO on regulating the blood glucose. In this study, with the acute peritoneal infection model of rats, we measured the blood glucose level, serum TNF-α, IL-6, insulin and NO level in order to study the association between glucose metabolism and these correlate factors.Methods: The experiment was formed by two parts. In the first part, rats were separately subjected to cecal ligation plus puncture(CLP), intraperitoneal injection of lipopolysaccharide (LPS) and CLP combine intraperitoneal injection of LPS to produce acute peritoneal infection. The blood glucose and TNF-α, IL-6, insulin were detected, insulin resistance index (IRI) was calculated to evaluate the extent of insulin resistance. In the second part, rats were subjected to cecal ligation plus puncture (CLP) to produce acute peritoneal infection model and then received intraperitoneal injection of L-arginine, lipopolysaccharide (LPS) and LPS plus LNNA. The level of Blood glucose, insulin and NO were detected.Result: IRI and blood glucose raised in the early stage of peritoneal infection and they have a positive correlation with TNF-αand IL-6, the coefficient correlation is 0.609 and 0.775 respectivly, while the raise of IL-6 persisted longer than TNF-α. Compared with CLP group, rats received intraperitoneal injection of L-arginine presented a higher level of NO and a lower level of blood glucose. LPS group presented a significant raise of NO but a higher level of blood glucose. While in the NNLA group, the hyperglycemia was relieved.Conclusion: Our results suggest that insulin resistance occurs in the early stage of acute peritoneal infection. Although there are differences of their action time, both TNF-αand IL-6 have an intimate relationship with insulin resistance. The raise of NO could prevent the hyperglycemia, but once the NO is overflowed, it may aggravate the hyperglycemia, indicating that the effect of NO is determined by its level.