Effects of obesity and gender on insulin receptor expression in liver of SHHF/Mcc-FAcp rats.
Effects of obesity and gender on insulin receptor expression in liver of SHHF/Mcc-FAcp rats.
复制标题
肥胖和性别对SHHF/Mcc-FAcp大鼠肝脏胰岛素受体表达的影响。
DOI：
10.1002/j.1550-8528.1995.tb00176.x
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Kissebah,AH
中科院分区：
文献类型：
--
作者：
Meier,DA;Hennes,MM;McCune,SA;Kissebah,AH
在SHHF/MCC-FAcprats(以前的SHR/MCC-cp)中，肥胖和男性协同调节高胰岛素血症、胰岛素抵抗和糖尿病易感性。我们以前的研究表明，性别和肥胖对肝细胞表面胰岛素结合和胰岛素清除有额外的调节作用。肝脏胰岛素受体(IR)通过内化和降解结合胰岛素，作为胰岛素清除的第一步。我们假设肥胖和性别对肝脏胰岛素结合和清除的协同作用源于这两个因素对肝脏IR表达的相互作用。为了解决IR在SHHF/MCC-FAcprats中的表达，我们通过Western blotting定量了洗涤剂溶解的肝匀浆中的IR蛋白水平，并通过溶液杂交/核糖核酸酶保护试验测定了IR mRNA的水平。肥胖使男性和女性的肝脏总IR含量分别下降了50%和68%。男性使瘦肉大鼠胰岛素抵抗蛋白含量降低24%，但对肥胖大鼠胰岛素抵抗蛋白含量无影响。性别和肥胖对肝脏IR mRNA含量均无影响。因此，肥胖似乎通过转录后机制影响肝脏IR蛋白含量和细胞表面结合；类似地，男性瘦大鼠通过不涉及Changi在mRNA水平上的机制降低IR蛋白水平和细胞表面结合。在肥胖大鼠中，男性的协同效应似乎涉及IR转导的变化，从而涉及细胞表面胰岛素结合和加工的变化。
In SHHF/Mcc‐FAcprats (formerly SHR/Mcc‐cp), obesity and male gender synergistically modulate hyperinsulinemia, insulin resistance and predisposition to diabetes. Our previous studies showed gender and obesity modulate hepatic cell surface insulin binding and insulin clearance additively. Hepatic insulin receptors (IR) bind insulin as a first step in insulin clearance through internalization and degradation. We hypothesize that the synergistic effects of obesity and gender on hepatic insulin binding and clearance result from interaction of these two factors on hepatic IR expression. To address IR expression in SHHF/Mcc‐FAcprats, we quantitated IR protein levels in detergent‐solubilized liver homogenates by Western blotting and IR mRNA levels by a solution hybridization/RNase protection assay. Obesity reduced total hepatic IR content in males and females, 50% and 68% respectively. Male gender reduced IR protein content 24% in lean, but had no effect on IR protein content in obese rats. Neither gender nor obesity affected hepatic IR mRNA content. Thus, obesity appears to affect hepatic IR protein content and cell surface binding through post‐transcriptional mechanisms; similarly, male gender in lean rats reduces IR protein levels and cell surfac binding through mechanisms not involving changi in mRNA levels. In obese rats, the synergistic effec of male gender appears to involve changes in IR tra ticking and consequently cell surface insulin bindin and processing.