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分离的人脂肪细胞中糖原合酶动力学:胰岛素对糖原合酶作用的体外模型

Glycogen synthase kinetics in isolated human adipocytes: an in vitro model for the effects of insulin on glycogen synthase.

作者信息

Madar Z, Bell J M, Mandarino L J

机构信息

Department of Biochemistry and Human Nutrition, Rehovot, Hebrew University of Jerusalem, Israel.

出版信息

Biochem Med Metab Biol. 1987 Dec;38(3):265-71. doi: 10.1016/0885-4505(87)90090-9.

DOI:10.1016/0885-4505(87)90090-9
PMID:3124871
Abstract

Glycogen synthase which catalyzes the incorporation of uridine dipophosphate glucose into glycogen is found in muscle, liver, and fat. The activity of this enzyme is increased by insulin through a dephosphorylation mechanism. Because of the critical role of glycogen synthase in glucose storage and overall glucose metabolism, it is important to assess the status of the activity of this enzyme in normal humans as well as in individuals with pathological conditions, such as non-insulin-dependent diabetes mellitus. However, in human subjects, studies of the regulation of glycogen synthase in vivo are time consuming and tedious. The present study was, therefore, undertaken to establish whether adipocytes isolated from subcutaneous adipose tissue biopsies from normal human subjects could be used to assess the effect of insulin in vitro on glycogen synthase activity. Regulation of glycogen synthase in human adipocytes by glucose 6-phosphate and uridine disphosphate glucose was found to be somewhat different than that reported for the regulation of this enzyme in tissues from other species. The adipocyte was found to be a sensitive model for insulin activation of this enzyme. Glycogen synthase was stimulated twofold by an insulin concentration of as low as 1 ng/ml, while half-maximal activation of enzyme activity occurred at 0.4 +/- 0.1 ng insulin/ml. The present studies indicate that the isolated human subcutaneous adipocyte may serve as a useful model for in vitro investigation of the effects of insulin on glycogen synthase.

摘要

催化尿苷二磷酸葡萄糖掺入糖原的糖原合酶存在于肌肉、肝脏和脂肪中。该酶的活性通过去磷酸化机制被胰岛素增强。由于糖原合酶在葡萄糖储存和整体葡萄糖代谢中起关键作用,因此评估该酶在正常人和患有诸如非胰岛素依赖型糖尿病等病理状况的个体中的活性状态非常重要。然而,在人体受试者中,体内糖原合酶调节的研究既耗时又繁琐。因此,本研究旨在确定从正常人体受试者皮下脂肪组织活检中分离出的脂肪细胞是否可用于在体外评估胰岛素对糖原合酶活性的影响。发现葡萄糖6 - 磷酸和尿苷二磷酸葡萄糖对人脂肪细胞中糖原合酶的调节与在其他物种组织中报道的该酶调节有所不同。脂肪细胞被发现是该酶胰岛素激活的敏感模型。胰岛素浓度低至1 ng/ml时,糖原合酶的活性被刺激两倍,而酶活性的半最大激活发生在0.4±0.1 ng胰岛素/ml。本研究表明,分离出的人皮下脂肪细胞可能是体外研究胰岛素对糖原合酶作用的有用模型。

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1
Glycogen synthase kinetics in isolated human adipocytes: an in vitro model for the effects of insulin on glycogen synthase.分离的人脂肪细胞中糖原合酶动力学:胰岛素对糖原合酶作用的体外模型
Biochem Med Metab Biol. 1987 Dec;38(3):265-71. doi: 10.1016/0885-4505(87)90090-9.
2
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Am J Physiol. 1984 Nov;247(5 Pt 1):E581-4. doi: 10.1152/ajpendo.1984.247.5.E581.
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Skeletal muscle glycogenolysis is more sensitive to insulin than is glucose transport/phosphorylation. Relation to the insulin-mediated inhibition of hepatic glucose production.骨骼肌糖原分解对胰岛素的敏感性高于葡萄糖转运/磷酸化。与胰岛素介导的肝葡萄糖生成抑制的关系。
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Acquired defects of glycogen synthase activity in cultured human skeletal muscle cells: influence of high glucose and insulin levels.培养的人骨骼肌细胞中糖原合酶活性的获得性缺陷:高葡萄糖和胰岛素水平的影响。
Diabetes. 1996 Apr;45(4):400-7. doi: 10.2337/diab.45.4.400.