EFFECT OF ALTERATIONS IN MEMBRANE LIPID UNSATURATION ON THE PROPERTIES OF THE INSULIN-RECEPTOR OF EHRLICH ASCITES-CELLS

EFFECT OF ALTERATIONS IN MEMBRANE LIPID UNSATURATION ON THE PROPERTIES OF THE INSULIN-RECEPTOR OF EHRLICH ASCITES-CELLS
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DOI:
10.1016/0005-2736(82)90318-2
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发表时间:
1982-01-01
期刊:
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子:
--
通讯作者:
SPECTOR, AA
SPECTOR, AA
中科院分区:
其他
文献类型:
--
作者:
GINSBERG, BH;JABOUR, J;SPECTOR, AA

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本文研究了在小鼠体内生长的埃利希腹水癌细胞质膜磷脂成分的改变及其对该细胞胰岛素受体特性的影响。埃利希细胞的胰岛素受体表现出哺乳动物胰岛素受体的所有结合特征:对胰岛素和胰岛素类似物的特异性、饱和性、稳态结合水平与温度的反比关系和负协同性。富含单不饱和脂肪酰基的细胞磷脂是通过动物的生长产生的,这些动物保持在富含椰子油的饮食中;富含多不饱和脂肪酰基的细胞磷脂是在喂食向日葵油的动物中产生的。胰岛素受体在正常细胞中以180,000个位点/细胞存在,但在富含单不饱和脂肪酸的细胞中降至125,000(P < 0.001),在富含多不饱和脂肪酸的细胞中升至386,000(P < 0.001)。正常细胞的亲和常数(.hivin.Ke和.hivin.Kf)为0.03和0.01 nM-1。富含单不饱和脂肪酸的细胞的这些亲和常数增加至0.06和0.03 nM-1,而在富含多不饱和脂肪酸的细胞中获得0.01和0.005 nM-1的值(所有比较P < 0.001)。因此,增加不饱和度的质膜磷脂,产生的饮食操作,与胰岛素受体数量的增加,但结合亲和力下降。相反,增加的饱和度的磷脂的质膜与受体数量的减少和亲和力的增加。结果可以解释的模型,其中胰岛素受体被假定为多聚体。
The phospholipid composition of the plasma membranes of Ehrlich ascites cells grown in mice was altered and the effects on the properties of the insulin receptor of this cell were studied. The insulin receptor of the Ehrlich cell demonstrated all of the binding characteristics of mammalian insulin receptors: specificity for insulin and insulin analogs, saturability, inverse relationship of steady-state binding levels to temperature and negative cooperativity. Cellular phospholipids enriched in monounsaturated fatty acyl groups were produced by growth in animals that were maintained on a diet rich in coconut oil; cellular phospholipids enriched in polyunsaturated fatty acyl groups were produced in animals fed sunflower oil. Insulin receptors were present in the normal cells at 180,000 sites/cell but this fell to 125,000 (P < 0.001) in cells enriched in monounsaturated fatty acids and rose to 386,000 (P < 0.001) in cells enriched in polyunsaturated fatty acids. The normal cells had affinity constants (.hivin.Ke and .hivin.Kf) of 0.03 and 0.01 nM-1. The cells enriched in monounsaturated fatty acids had an increase in these affinity constants to 0.06 and 0.03 nM-1 whereas values of 0.01 and 0.005 nM-1 were obtained in the cells enriched in polyunsaturated fatty acids (all comparison P < 0.001). Thus, increased unsaturation of plasma membrane phospholipids, produced by dietary manipulations, was associated with an increase in insulin receptor number but a decrease in binding affinity. In contrast, increased saturation of the phospholipids of the plasma membrane was associated with a decrease in receptor number and an increase in affinity. The results can be explained by a model in which the insulin receptor is assumed to be multimeric.