Zhu Bo, Li Chen-zhong, Qian Yi, Pan Yong-hua, Li Jia, Zhang Yan, Xue Yao-ming
Department of Endocrinology and Metabolism, Southern Medical University, Guangzhou , China.
Nan Fang Yi Ke Da Xue Xue Bao. 2011 May;31(5):782-6.
To investigate the effect of adiponectin (APN) on the insulin pathway in the liver of OLETF rats and explore its molecular mechanism.
Twenty 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.
The 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).
APN 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.
研究脂联素（APN）对OLETF大鼠肝脏胰岛素信号通路的影响，并探讨其分子机制。
分别于8周龄和32周龄处死20只雄性OLETF大鼠和10只雄性LETO大鼠，检测空腹血糖、血清胰岛素、脂联素和血脂水平。采用酶联免疫吸附测定（ELISA）、蛋白质免疫印迹法（Western blotting）或免疫组织化学法检测肝脏组织中的APN、胰岛素受体底物-1（IRS-1）的磷酸化酪氨酸、IKKβ和核因子κB（NF-κB）。
自8周龄起，OLETF大鼠血浆脂联素水平显著低于LETO大鼠（P<0.01）。32周龄时，OLETF大鼠血脂水平显著升高（P<0.05），且与血浆脂联素呈负相关（P<0.01）。在8周龄和32周龄时，OLETF大鼠肝脏中的APN、磷酸化IRS-1（py-IRS-1）、IKKβ和NF-κB水平与LETO大鼠相比均有显著差异。32周龄时，两种大鼠的APN水平均与NF-κB和py-IRS-1水平相关（P<0.01）。
APN可能通过IKK/NFκB途径降低IRS-1的酪氨酸磷酸化水平，抑制肝脏胰岛素信号通路，这可能是导致高脂血症、高血糖及2型糖尿病发生发展的原因之一。
