Kaempferol alleviates insulin resistance via hepatic IKK/NF-κB signal in type 2 diabetic rats

Int Immunopharmacol. 2015 Sep;28(1):744-50. doi: 10.1016/j.intimp.2015.07.018. Epub 2015 Aug 9.

Abstract

Recent studies show that inflammation underlies the metabolic disorders of insulin resistance and type 2 diabetes mellitus. Since kaempferol, a naturally occurring flavonoid, has been described to have potent anti-inflammatory properties, we investigated whether kaempferol could ameliorate insulin resistance through inhibiting inflammatory responses. The model of diabetic rat was induced by 6-week high-fat diet plus streptozotocin. Animals were orally treated with kaempferol (50 or 150 mg/kg) and aspirin (100mg/kg) for 10 weeks. The results showed that kaempferol ameliorated blood lipids and insulin in an dose-dependent manner. Kaempferol effectively restored insulin resistance induced alteration of glucose disposal by using an insulin tolerance test and the euglycemic-hyperinsulinemic clamp method. Western blotting results showed that KPF inhibited the phosphorylation of insulin receptor substrate-1 (IRS-1), IkB kinase α (IKKα) and IkB kinase β (IKKβ). These effects were accompanied with reduction in nucleic and cytosol levels of nuclear factor kappa-β (NF-κB), and further tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels. Aspirin had similar effects. These results provide in vivo evidence that kaempferol-mediated down-regulation of IKK and subsequent inhibition of NF-κB pathway activation may be associated with the reduction of hepatic inflammatory lesions, which is contributing to the improvement of insulin signaling defect in diabetes.

Keywords: Inflammation; Insulin resistance; Kaempferol; Nuclear factor kappa-β; Rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Blood Glucose / analysis
  • Diabetes Mellitus / drug therapy*
  • Diabetes Mellitus / metabolism
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / metabolism
  • Dose-Response Relationship, Drug
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / therapeutic use*
  • I-kappa B Kinase / metabolism*
  • Infant, Newborn, Diseases / drug therapy*
  • Infant, Newborn, Diseases / metabolism
  • Insulin / blood
  • Insulin Resistance*
  • Kaempferols / administration & dosage
  • Kaempferols / therapeutic use*
  • Liver / drug effects*
  • Liver / immunology
  • Liver / metabolism
  • Male
  • NF-kappa B / metabolism*
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Streptozocin / pharmacology

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Kaempferols
  • NF-kappa B
  • Streptozocin
  • kaempferol
  • I-kappa B Kinase

Supplementary concepts

  • Diabetes Mellitus, Transient Neonatal, 2