Effect of aspirin on the expression of hepatocyte NF-κB and serum TNF-α in streptozotocin-induced type 2 diabetic rats

J Korean Med Sci. 2011 Jun;26(6):765-70. doi: 10.3346/jkms.2011.26.6.765. Epub 2011 May 18.

Abstract

Aspirin is a kind of anti-inflammatory drug and may be used to reverse hyperglycemia, hyperinsulinemia, and dyslipidemia by improving insulin resistance. We hypothesized that aspirin improves insulin resistance in type 2 diabetes by inhibiting hepatic nuclear factor kappa-β (NF-κB) activation and serum tumor necrosis factor-α (TNF-α). Adult male Wistar rats were randomly divided into four groups: control, untreated diabetic, diabetic treated with metformin (100 mg/kg/day), and diabetic treated with aspirin (120 mg/kg/day). Diabetes was induced by high-fat feeding and a low dose of streptozotocin (30 mg/kg). After treatment, plasma glucose, insulin, lipids, free fatty acids (FFAs) concentrations and serum TNF-α were determined. The expression of NF-κB in hepatocytes was analyzed by immunohistochemistry and western blot. The results showed administration of aspirin caused no significant lowering in fasting glucose level but significant reduction of hepatic NF-κB expression and serum TNF-α level with improved insulin resistance compared to the diabetic group. The relevant analysis showed positive correlation between the expression of homeostasis model assessment-insulin resistance (HOMA-IR) and NF-κB (r = 0.799, P < 0.01); HOMA-IR and serum TNF-α (r = 0.790, P < 0.01). It is concluded that aspirin improves insulin resistance by inhibiting hepatic NF-κB activation and TNF-α level in streptozotocin-induced type 2 diabetic rats.

Keywords: Aspirin; Inflammation; Insulin Resistance.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Aspirin / pharmacology*
  • Blood Glucose / analysis
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / metabolism*
  • Fatty Acids, Nonesterified / blood
  • Hypoglycemic Agents / pharmacology*
  • Insulin / blood
  • Insulin Resistance
  • Liver / metabolism
  • Male
  • Metformin / therapeutic use
  • NF-kappa B / metabolism*
  • Rats
  • Rats, Wistar
  • Tumor Necrosis Factor-alpha / blood*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Blood Glucose
  • Fatty Acids, Nonesterified
  • Hypoglycemic Agents
  • Insulin
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Metformin
  • Aspirin