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低胰岛素血症性糖尿病中肝脏胰岛素受体上调的机制。

The mechanisms of up-regulation of the hepatic insulin receptor in hypoinsulinemic diabetes mellitus.

作者信息

Salhanick A I, West H, Amatruda J M

出版信息

J Biol Chem. 1985 Dec 25;260(30):16232-6.

PMID:3905811
Abstract

The mechanism underlying the increased insulin binding found in hepatic plasma membranes from streptozotocin-diabetic rats was evaluated by measuring insulin binding to intact and Triton X-100-soluble extracts of plasma membranes prepared from the livers of control rats and rats administered streptozotocin (85 mg/kg). In addition, to assess whether the cellular content of hepatic insulin receptors is also increased in diabetic animals, we measured insulin-binding activity in intact and soluble extracts of total hepatic cellular membrane preparations (100,000 X g cellular pellets). The data indicate that while insulin binding is increased (52 +/- 3%) in intact hepatic plasma membranes from diabetic rats compared to control rats, there is no comparable increase in insulin binding in intact total cellular membranes or in Triton X-100-soluble extracts of plasma membranes or total cellular membranes. We therefore conclude that the enhanced insulin binding found in the livers of diabetic rats is the result of a local redistribution of plasma membrane insulin receptors from cryptic to exposed sites. Finally, the data suggest the presence of a negative modulator of insulin-binding affinity in intact plasma and total cellular membranes.

摘要

通过测量胰岛素与从对照大鼠和注射链脲佐菌素(85mg/kg)的大鼠肝脏制备的完整质膜以及Triton X-100可溶性质膜提取物的结合,评估了链脲佐菌素诱导的糖尿病大鼠肝质膜中胰岛素结合增加的潜在机制。此外,为了评估糖尿病动物肝脏胰岛素受体的细胞含量是否也增加,我们测量了完整的和可溶的全肝细胞膜制剂(100,000×g细胞沉淀)中的胰岛素结合活性。数据表明,与对照大鼠相比,糖尿病大鼠完整肝质膜中的胰岛素结合增加(52±3%),但完整全细胞膜或质膜或全细胞膜的Triton X-100可溶提取物中的胰岛素结合没有相应增加。因此,我们得出结论,糖尿病大鼠肝脏中增强的胰岛素结合是质膜胰岛素受体从隐匿部位向暴露部位局部重新分布的结果。最后,数据表明完整质膜和全细胞膜中存在胰岛素结合亲和力的负调节剂。

相似文献

1
The mechanisms of up-regulation of the hepatic insulin receptor in hypoinsulinemic diabetes mellitus.低胰岛素血症性糖尿病中肝脏胰岛素受体上调的机制。
J Biol Chem. 1985 Dec 25;260(30):16232-6.
2
[Specific 125I-insulin binding by hepatocyte plasma membranes and nuclear envelopes in experimental hyperinsulinemia, alloxan diabetes and starvation].[实验性高胰岛素血症、四氧嘧啶糖尿病和饥饿状态下肝细胞质膜与核膜的特异性125I-胰岛素结合]
Tsitologiia. 1984 Jul;26(7):818-25.
3
[Binding properties of insulin receptors in adipose tissue and hepatic plasma membranes in rats during fasting and in alloxan diabetes].[禁食及四氧嘧啶糖尿病大鼠脂肪组织与肝细胞膜中胰岛素受体的结合特性]
Probl Endokrinol (Mosk). 1986 May-Jun;32(3):54-9.
4
Increased affinity of insulin receptor on hepatocytes from streptozotocin-induced diabetic rats.链脲佐菌素诱导的糖尿病大鼠肝细胞上胰岛素受体亲和力增加。
Endocrinol Jpn. 1984 Jun;31(3):235-43. doi: 10.1507/endocrj1954.31.235.
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Effect of alloxan diabetes and phenformin on insulin binding with liver plasma membrane receptors.四氧嘧啶糖尿病和苯乙双胍对胰岛素与肝细胞膜受体结合的影响。
Jpn J Exp Med. 1984 Oct;54(5):189-93.
6
[Additive nature of the stimulating effects of alloxan diabetes and fasting on the specific binding of insulin with its receptors in the plasma membranes of adipose and hepatic cells in the rat].[四氧嘧啶糖尿病和禁食对大鼠脂肪细胞和肝细胞质膜中胰岛素与其受体特异性结合的刺激作用的相加性质]
Vopr Med Khim. 1985 Mar-Apr;31(2):46-51.
7
Regulation of rat liver plasma membrane and intracellular insulin binding sites during diabetes, liver regeneration, and hyperinsulinism: radiolabeled hormone binding and electron microscopic autoradiograph studies.糖尿病、肝脏再生和高胰岛素血症期间大鼠肝细胞膜及细胞内胰岛素结合位点的调节:放射性标记激素结合及电子显微镜放射自显影研究
Adv Biochem Psychopharmacol. 1980;21:499-506.
8
[Effect of experimental hyperinsulinemia on the insulin receptor activity of the plasma membranes of the fatty and liver tissue from rats with disturbed liver innervation].[实验性高胰岛素血症对肝脏神经支配紊乱大鼠脂肪组织和肝脏组织质膜胰岛素受体活性的影响]
Biull Eksp Biol Med. 1982 May;93(5):52-5.
9
Insulin binding to liver plasma membranes from rats rendered diabetic by alloxan. A kinetic demonstration of two classes of binding sites in equilibrium with each other.胰岛素与经四氧嘧啶诱导成糖尿病的大鼠肝脏质膜的结合。两类相互处于平衡状态的结合位点的动力学证明。
Biochem J. 1982 Jan 15;202(1):259-62. doi: 10.1042/bj2020259.
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Mechanisms of up-regulation of the liver insulin receptor in chronically hypoinsulinemic rats: assessment of receptor endocytosis.
Mol Cell Endocrinol. 1991 Dec;82(2-3):159-64. doi: 10.1016/0303-7207(91)90027-p.