Kaempferol alleviates insulin resistance via hepatic IKK/NF-κB signal in type 2 diabetic rats.
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.
Clinical Pharmacology Laboratory, Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People's Republic of China.
Cheng
C
Luo
Clinical Pharmacology Laboratory, Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People's Republic of China.
Hui
H
Yang
Clinical Pharmacology Laboratory, Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People's Republic of China.
Chengyong
C
Tang
Clinical Pharmacology Laboratory, Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People's Republic of China.
Gaoqiong
G
Yao
Clinical Pharmacology Laboratory, Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People's Republic of China.
Lingxi
L
Kong
Clinical Pharmacology Laboratory, Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People's Republic of China.
Haixia
H
He
Clinical Pharmacology Laboratory, Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People's Republic of China. Electronic address: zhouyuanda001@163.com.
Yuanda
Y
Zhou
D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D051550:I-kappa B Kinase / Q000378:metabolism*; D007232:Infant, Newborn, Diseases / Q000188:drug therapy* / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D044949:Kaempferols / Q000008:administration & dosage / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013311:Streptozocin / Q000494:pharmacology
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D044949:Kaempferols; D016328:NF-kappa B; D013311:Streptozocin; C006552:kaempferol; D051550:I-kappa B Kinase
Inflammation; Insulin resistance; Kaempferol; Nuclear factor kappa-β; Rats