Adiponectin decreases insulin receptor substrate-1 phosphorylation in the liver of OLETF rats possibly through nuclear factor-κB signaling pathway.
- Author:
Bo ZHU
1
;
Chen-zhong LI
;
Yi QIAN
;
Yong-hua PAN
;
Jia LI
;
Yan ZHANG
;
Yao-ming XUE
Author Information
- Publication Type:Journal Article
- MeSH: Adiponectin; pharmacology; Animals; Diabetes Mellitus, Type 2; metabolism; Insulin; metabolism; Insulin Receptor Substrate Proteins; metabolism; Liver; drug effects; metabolism; Male; Phosphorylation; Rats; Rats, Inbred OLETF; Signal Transduction; drug effects
- From: Journal of Southern Medical University 2011;31(5):782-786
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the effect of adiponectin (APN) on the insulin pathway in the liver of OLETF rats and explore its molecular mechanism.
METHODSTwenty male OLETF rats and 10 male LETO rats were sacrificed at 8 and 32 weeks of age to examine the fasting blood glucose, serum insulin, adiponectin and blood lipid profiles. The APN, phosphotyrosine of insulin receptor substrate-1 (IRS-1), IKKβ and nuclear-κB (NF-κB) in the liver tissue were determined using ELISA, Western blotting or immunohistochemistry.
RESULTSThe plasma adiponectin level in OLETF rats was significantly lower than that of LETO rats since 8 weeks of age (P<0.01). At 32 weeks of age, the blood lipid levels of OLETF rats increased significantly (P<0.05) with inverse correlations to plasma adiponectin (P<0.01). The liver APN, py-IRS-1, IKKβ and NF-κB levels in OLETF rats differed significantly from those of LETO rats at both 8 and 32 weeks. At 32 weeks of age, the APN level of both rats were correlated to the levels of NF-κB and py-IRS-1 (P<0.01).
CONCLUSIONAPN may decrease tyrosine phosphorylation of IRS-1 via the IKK/NFκB pathway and inhibit insulin signaling pathway in the liver, which contributes to hyperlipidemia, hyperglycemia and development of type 2 diabetes.
