| IntroductionIn the past few decades, type 2 diabetes mellitus (T2DM) and metablic syndrome have rapidly increased in the world, resulting from the interaction between a subject's genetic makeup and lifestyle. Insulin resistance is the "common soil", multiplying T2DM and metablic syndrome. During the development of insulin resistance, there is chronic non-specific inflammation, including many inflammatory cytokines, which mainly originating from adipose tissue. Adiponectin, exclusively derived from adipose tissue, could increase insulin sensitivity. The subclinic inflammation may lead to hypoadiponectin in insulin resistance. Nuclear transcription factor-kappa B (NF-κB) inhibitor kinase (IKK)/NF-κB is one of the key inflammatory signal transduction iter. To approach the relationship between IKK/NF-κB and adiponectin, may conduce to illuminate the molecular mechanism of insulin resistance, providing a novel approach to treat hypoadiponectin.ObjectiveTo observe the relationship between adiponectin mRNA expression of visceral adipose tissue and IKK/NF-κB expression of insulin target tissue in insulin resistant rats. To approach the intervenient effect of simvastatin on the expression of adiponectin and IKK/NF-κB, as well as the influence on the insulin resistance.MethodsInsulin resistant rat model was induced by high-fat diet feeding. Thirty-five male Wistar rats were randomly divided into two groups feeding either basic chow (NF group, n=15) or high-fat diet (HF group, n=20) for 10 weeks, then assessed by euglycemic-hyperinsulinemia clamp technique (EHCT). And the rats in HF group were randomly divided into two groups, simvastatin intervention group (HFS, n=5) and not simvastatin intervention group (HFN, n=5). The rats in HFS group were fed with simvastatin 10mg·kg-1·d-1 in gavage. After 5 weeks intervention treatmeant, serum lipid assay was performed with enzymatic measure, free fatty acid (FFA) was tested with colorimetry, serum adiponectin and insulin was determined by enzyme linked immunosorbent assay (ELISA), the expression of adiponectin and IKK mRNA in tissue was tested with reverse transcription polymerase chain reaction (RT-PCR), and the NF-κBp65 expression in liver was tested with Western blotting.Results(1)High-fat diet in which fat affording 71% caloric, induced insulin resistant rat model. The average glucose infusion rate (GIR) during 60～120min of EHCT in HF group decreased significantly compared with NF group. The percentage of epididymis adipose mass in body weight, fasted serum insulin, triglyceride and FFA in HF group increased significantly compared with NF group. Serum adiponectin level and insulin sensitivity index (ISI) in HF group decreased significantly compared with NF group.(2) Compared with NF group, the adiponectin mRNA expression of visceral adipose tissue in HF group decreased significantly, the IKK mRNA expression of visceral adipose tissue, liver and muscle in HF group increased significantly, the NF-κBp65 expression of liver in HF group increased significantly. The adiponectin and IKK mRNA expression was negative correlation.(3)There were no obvious difference on the adiponectin mRNA expression of adipose tissue between HFS group and HFN group, but they decreased significantly compared with basic chow group (NFC group). The IKK mRNA expression of adipose tissue and liver, and the NF-κBp65 expression of liver in HFS group decreased significantly compared with HFN group, though was not obviously different from NFC group. There were no obvious difference on ISI between HFS group and HFN group, but they decreased significantly compared with NFC group. ConclusionIKK may be the key enzyme inducing the decrease of adiponectin mRNA expression in adipose tissue of insulin resistant rat. Simvastatin could inhibit the activation of IKK/NF-κB in insulin target tissue of insulin resistant rat, which may benefit improving local insulin resistance in target tissue. But simvatatin couldn't augment the expression of adiponectin mRNA in adipose tissue, and couldn't significantly improve systemic insulin resistance.
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