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胰岛素分泌颗粒生物发生与胰岛素原加工内肽酶

Insulin secretory granule biogenesis and the proinsulin-processing endopeptidases.

作者信息

Hutton J C

机构信息

Department of Clinical Biochemistry, Addenbrooke's Hospital, Cambridge, UK.

出版信息

Diabetologia. 1994 Sep;37 Suppl 2:S48-56. doi: 10.1007/BF00400826.

DOI:10.1007/BF00400826
PMID:7821740
Abstract

The insulin storage granule of the pancreatic beta cell is assembled within the trans Golgi network from around 50 or so gene products many of which are synthesized coordinately with the major component, proinsulin. An important contribution to our understanding of the regulation of this process has come from studies of the post-translational processing of proinsulin and of other proteins which are stored in the granule, particularly the processing enzymes themselves. The present review focusses on recent insights into the molecular nature of the processing machinery, and the granule Ca(2+)-dependent subtilisin-related endopeptidases which catalyse the initial rate-limiting step in the enzymic conversion of proinsulin.

摘要

胰腺β细胞的胰岛素储存颗粒是在反式高尔基体网络中由大约50种左右的基因产物组装而成,其中许多基因产物与主要成分胰岛素原协同合成。对胰岛素原和其他储存于颗粒中的蛋白质(尤其是加工酶本身)进行的翻译后加工研究,为我们理解这一过程的调控做出了重要贡献。本综述重点关注加工机制的分子本质以及颗粒中依赖钙离子的枯草杆菌蛋白酶相关内肽酶的最新见解,这些酶催化胰岛素原酶促转化中的初始限速步骤。

相似文献

1
Insulin secretory granule biogenesis and the proinsulin-processing endopeptidases.胰岛素分泌颗粒生物发生与胰岛素原加工内肽酶
Diabetologia. 1994 Sep;37 Suppl 2:S48-56. doi: 10.1007/BF00400826.
2
Proinsulin processing in the regulated and the constitutive secretory pathway.胰岛素原在调节性分泌途径和组成型分泌途径中的加工过程。
Diabetologia. 1994 Sep;37 Suppl 2:S65-72. doi: 10.1007/BF00400828.
3
Preferential cleavage of des-31,32-proinsulin over intact proinsulin by the insulin secretory granule type II endopeptidase. Implication of a favored route for prohormone processing.胰岛素分泌颗粒II型内肽酶对去31,32-胰岛素原的切割优先于完整胰岛素原。这暗示了前激素加工的一条有利途径。
J Biol Chem. 1992 Nov 15;267(32):22719-27.
4
Proprotein-processing endopeptidases of the insulin secretory granule.
Enzyme. 1991;45(5-6):301-13. doi: 10.1159/000468903.
5
Intracellular transport of proinsulin in pancreatic beta-cells. Structural maturation probed by disulfide accessibility.胰岛素原在胰腺β细胞中的细胞内运输。通过二硫键可及性探究结构成熟过程。
J Biol Chem. 1995 Sep 1;270(35):20417-23. doi: 10.1074/jbc.270.35.20417.
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Proalbumin to albumin conversion by a proinsulin processing endopeptidase of insulin secretory granules.胰岛素分泌颗粒的胰岛素原加工内肽酶将前白蛋白转化为白蛋白。
J Biol Chem. 1989 Aug 25;264(24):14240-5.
7
Des-(27-31)C-peptide. A novel secretory product of the rat pancreatic beta cell produced by truncation of proinsulin connecting peptide in secretory granules.去(27 - 31)C肽。一种由大鼠胰腺β细胞在分泌颗粒中胰岛素原连接肽截短产生的新型分泌产物。
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What beta-cell defect could lead to hyperproinsulinemia in NIDDM? Some clues from recent advances made in understanding the proinsulin-processing mechanism.何种β细胞缺陷会导致非胰岛素依赖型糖尿病(NIDDM)患者出现高胰岛素原血症?从近期对胰岛素原加工机制的理解进展中可找到一些线索。
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Stimulation by ATP of proinsulin to insulin conversion in isolated rat pancreatic islet secretory granules. Association with the ATP-dependent proton pump.三磷酸腺苷(ATP)对分离的大鼠胰岛分泌颗粒中胰岛素原向胰岛素转化的刺激作用。与ATP依赖性质子泵的关联。
J Biol Chem. 1987 Aug 5;262(22):10712-7.
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Comparison of prohormone-processing activities in islet microsomes and secretory granules: evidence for distinct converting enzymes for separate islet prosomatostatins.胰岛微粒体和分泌颗粒中激素原加工活性的比较:不同胰岛前生长抑素存在不同转化酶的证据
J Cell Biol. 1984 Aug;99(2):578-87. doi: 10.1083/jcb.99.2.578.

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Secretory stimuli distinctly regulate insulin secretory granule maturation through structural remodeling.分泌刺激通过结构重塑显著调节胰岛素分泌颗粒的成熟。
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Changes in Cells Associated with Insulin Resistance.与胰岛素抵抗相关的细胞变化。
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From glucose sensing to exocytosis: takes from maturity onset diabetes of the young.从葡萄糖感应到胞吐作用:从青年发病的成年型糖尿病说起。

本文引用的文献

1
Protein sorting and secretion granule formation in regulated secretory cells.调节性分泌细胞中的蛋白质分选与分泌颗粒形成
Trends Cell Biol. 1992 Nov;2(11):327-31. doi: 10.1016/0962-8924(92)90181-l.
2
Identification and functional expression of a new member of the mammalian Kex2-like processing endoprotease family: its striking structural similarity to PACE4.哺乳动物类Kex2样加工内切蛋白酶家族一个新成员的鉴定与功能表达:其与PACE4显著的结构相似性。
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The biosynthesis of the subtilisin-related proprotein convertase PC3, but no that of the PC2 convertase, is regulated by glucose in parallel to proinsulin biosynthesis in rat pancreatic islets.
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Insulin: A connection between pancreatic β cells and the hypothalamus.胰岛素:胰腺β细胞与下丘脑之间的联系。
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Cholesterol Redistribution in Pancreatic β-Cells: A Flexible Path to Regulate Insulin Secretion.胆固醇在胰腺β细胞中的重分布:调节胰岛素分泌的一种灵活途径。
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Isolation and Proteomics of the Insulin Secretory Granule.胰岛素分泌颗粒的分离与蛋白质组学
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Characterization of Insulin-Producing β-Cell Spheroids.胰岛素分泌β细胞球体的表征
Front Cell Dev Biol. 2021 Jan 28;8:623889. doi: 10.3389/fcell.2020.623889. eCollection 2020.
8
Normal and defective pathways in biogenesis and maintenance of the insulin storage pool.胰岛素储存池生物发生和维持的正常和缺陷途径。
J Clin Invest. 2021 Jan 19;131(2). doi: 10.1172/JCI142240.
9
Insulin: Trigger and Target of Renal Functions.胰岛素:肾脏功能的触发因素与作用靶点
Front Cell Dev Biol. 2020 Jul 29;8:519. doi: 10.3389/fcell.2020.00519. eCollection 2020.
10
The cell biology of systemic insulin function.系统性胰岛素功能的细胞生物学。
J Cell Biol. 2018 Jul 2;217(7):2273-2289. doi: 10.1083/jcb.201802095. Epub 2018 Apr 5.
在大鼠胰岛中,枯草杆菌蛋白酶相关的前蛋白转化酶PC3的生物合成与胰岛素原生物合成平行受到葡萄糖的调节,但PC2转化酶的生物合成则不然。
J Biol Chem. 1993 Feb 25;268(6):4276-80.
4
(Pro)insulin associates with Golgi membranes of pancreatic B cells.(前)胰岛素与胰腺β细胞的高尔基体膜结合。
Proc Natl Acad Sci U S A. 1984 Nov;81(21):6743-6. doi: 10.1073/pnas.81.21.6743.
5
Pancreatic B-cells secrete a range of novel peptides besides insulin.胰腺β细胞除了分泌胰岛素外,还分泌一系列新型肽。
Biochim Biophys Acta. 1984 Apr 16;803(4):342-5. doi: 10.1016/0167-4889(84)90127-7.
6
Secretory granules.分泌颗粒
Experientia. 1984 Oct 15;40(10):1091-8. doi: 10.1007/BF01971456.
7
The internal pH and membrane potential of the insulin-secretory granule.胰岛素分泌颗粒的内部pH值和膜电位。
Biochem J. 1982 Apr 15;204(1):171-8. doi: 10.1042/bj2040171.
8
Membranes of the adrenal medulla. Behaviour of insoluble proteins of chromaffin granules on gel electrophoresis.肾上腺髓质的膜。嗜铬粒蛋白不溶性蛋白在凝胶电泳上的行为。
Biochem J. 1970 Jun;118(2):303-10. doi: 10.1042/bj1180303.
9
Direct identification of prohormone conversion site in insulin-secreting cells.胰岛素分泌细胞中激素原转化位点的直接鉴定。
Cell. 1985 Sep;42(2):671-81. doi: 10.1016/0092-8674(85)90124-2.
10
Conversion of proinsulin to insulin occurs coordinately with acidification of maturing secretory vesicles.胰岛素原向胰岛素的转化与成熟分泌小泡的酸化同时发生。
J Cell Biol. 1986 Dec;103(6 Pt 1):2273-81. doi: 10.1083/jcb.103.6.2273.