J Korean Med Sci.  2011 Jun;26(6):765-770. 10.3346/jkms.2011.26.6.765.

Effect of Aspirin on the Expression of Hepatocyte NF-kappaB and Serum TNF-alpha in Streptozotocin-Induced Type 2 Diabetic Rats

Affiliations
  • 1Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China. sxdfriend@sina.com
  • 2Department of Pathology, 401 Hospital of Chinese People's Liberation Army, Qingdao, China.
  • 3Department of Laboratory Medicine, Qingdao Municipal Hospital, Qingdao, China.

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-beta (NF-kappaB) activation and serum tumor necrosis factor-alpha (TNF-alpha). 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-alpha were determined. The expression of NF-kappaB 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-kappaB expression and serum TNF-alpha 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-kappaB (r = 0.799, P < 0.01); HOMA-IR and serum TNF-alpha (r = 0.790, P < 0.01). It is concluded that aspirin improves insulin resistance by inhibiting hepatic NF-kappaB activation and TNF-alpha level in streptozotocin-induced type 2 diabetic rats.

Keyword

Inflammation; Insulin Resistance; Aspirin

MeSH Terms

Animals
Anti-Inflammatory Agents, Non-Steroidal/*pharmacology
Aspirin/*pharmacology
Blood Glucose/analysis
Diabetes Mellitus, Experimental/blood/chemically induced/*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
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