Glucagon receptor of human liver. Studies of its molecular weight and binding properties, and its ability to activate hepatic adenylyl cyclase of non-obese and obese subjects.
Glucagon receptor of human liver. Studies of its molecular weight and binding properties, and its ability to activate hepatic adenylyl cyclase of non-obese and obese subjects.
复制标题
人肝脏的胰高血糖素受体。
DOI：
10.1172/jci111713
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
Arner,P
中科院分区：
文献类型：
--
作者：
Livingston,JN;Einarsson,K;Backman,L;Ewerth,S;Arner,P
在6名胰岛素和血浆胰高血糖素水平升高的非肥胖和6名肥胖受试者中研究了人肝膜的胰高血糖素受体和腺苷酸环化酶系统。通过Scatchard的方法对特异性胰高血糖素结合进行的分析表明，解离常数为2-3 nM的线性（单组分）图，并且在低激素浓度下的结合对三磷酸鸟苷（GTP）敏感。胰高血糖素受体的分子量为63，000 D，通过亲和标记程序和十二烷基硫酸钠凝胶电泳测定。该结构的亲和标记对胰高血糖素具有特异性，并被GTP抑制。胰高血糖素刺激产生环磷酸腺苷（cAMP）的人膜与半最大激活引起的6 nM激素。人环化酶系统需要GTP来促进最佳胰高血糖素反应。NaF（10 mM）也激活环化酶系统，并产生与最大胰高血糖素激活相同的反应幅度。使用胰高血糖素（5 nM和1 μ M）和NaF（10 mM）对非肥胖和肥胖受试者的肝脏腺苷酸环化酶系统进行比较。两组之间cAMP产生无显著差异，无论用于激活酶的试剂如何。这些发现与胰高血糖素结合研究一致，表明两组膜中的结合活性量相似。此外，受试者的年龄或性别对腺苷酸环化酶反应没有影响。总之，人肝膜含有胰高血糖素受体和腺苷酸环化酶系统，其与动物肝脏中充分研究的系统密切对应。人类肥胖症的这一系统并不因这种代谢紊乱中血浆胰高血糖素升高约2倍而改变。图片
The glucagon receptor and the adenylyl cyclase system of human liver membranes were studied in six non-obese and six obese subjects who had elevated insulin and plasma glucagon levels. Analysis of specific glucagon binding by the method of Scatchard demonstrated a linear (monocomponent) plot with a dissociation constant of 2-3 nM, and the binding at low hormone concentrations was sensitive to guanosine triphosphate (GTP). The molecular weight of the glucagon receptor was 63,000 D as determined by an affinity labeling procedure and sodium dodecyl sulfate gel electrophoresis. Affinity labeling of this structure was specific for glucagon and inhibited by GTP. Glucagon stimulated the production of cyclic adenosine monophosphate (cAMP) by human membranes with half-maximal activation elicited by 6 nM hormone. The human cyclase system required GTP to facilitate an optimal glucagon response. NaF (10 mM) also activated the cyclase system and produced the same magnitude of response as maximum glucagon activation. A comparison of the liver adenylyl cyclase system of non-obese and obese subjects was made using glucagon (5 nM and 1 microM) and NaF (10 mM). No significant differences in cAMP production were noted between the two groups, regardless of the agent used to activate the enzyme. These findings agree with the glucagon binding studies that showed similar amounts of binding activity in the membranes from the two groups. Also, there was no influence of either age or sex of the subjects on the adenylyl cyclase response. In conclusion, human liver membranes contain a glucagon receptor and an adenylyl cyclase system that correspond closely to the well-studied system in animal liver. This system in human obesity is not altered by the approximately twofold elevation in plasma glucagon that occurs in this metabolic disorder.Images