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经灌注的胰岛素瘤细胞释放胰岛素的动力学:葡萄糖、福斯可林、亮氨酸、钡和茶碱的作用。

Dynamics of insulin release by perifused insulin-producing tumoral cells: effects of glucose, forskolin, leucine, barium and theophylline.

作者信息

Leclercq-Meyer V, Giroix M H, Sener A, Marchand J, Malaisse W J

机构信息

Laboratory of Experimental Medicine, Brussels Free University, Belgium.

出版信息

Int J Pancreatol. 1988 Jan-Feb;3(1):17-31. doi: 10.1007/BF02788220.

DOI:10.1007/BF02788220
PMID:3280704
Abstract

Perifused tumoral insulin-producing cells, of the RINm5F line, display a high basal insulin output relative to their hormonal content. D-Glucose (2.8 or 16.7 mmol/l) causes a modest and monophasic increase in insulin output. The secretory response to D-glucose (1.4 to 16.7 mmol/l) is enhanced by forskolin, which exerts little effect in the absence of exogenous nutrient. L-Leucine (10.0 mmol/l) also stimulates insulin release from the perifused cells. The secretory response to these nutrient secretagogues in much less marked, however, than that evoked, in the absence of Ca2+, by the association of Ba2+ and theophylline. It is concluded that the dynamics of insulin release by the tumoral cells, when compared to that of normal islet cells, are characterized by several anomalies, including a high basal ratio between secretion and content, a low threshold (less than or equal to 1.4 mmol/l) in the secretory response to D-glucose, and a lesser responsiveness to nutrient than nonnutrient secretagogues.

摘要

用RINm5F细胞系建立的灌流肿瘤胰岛素分泌细胞,相对于其激素含量,具有较高的基础胰岛素分泌量。D-葡萄糖(2.8或16.7 mmol/L)可引起胰岛素分泌适度的单相增加。福斯可林可增强对D-葡萄糖(1.4至16.7 mmol/L)的分泌反应,在无外源营养物时其作用甚微。L-亮氨酸(10.0 mmol/L)也可刺激灌流细胞释放胰岛素。然而,这些营养性促分泌剂引起的分泌反应,远不如在无Ca2+时Ba2+与茶碱联合引起的分泌反应明显。结论是,与正常胰岛细胞相比,肿瘤细胞胰岛素释放的动力学具有若干异常特征,包括分泌与含量之间的基础比率较高、对D-葡萄糖分泌反应的阈值较低(小于或等于1.4 mmol/L)以及对营养性促分泌剂的反应性低于非营养性促分泌剂。

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本文引用的文献

1
Glucose-induced insulin release depends on functional cooperation between islet cells.葡萄糖诱导的胰岛素释放取决于胰岛细胞之间的功能协作。
Proc Natl Acad Sci U S A. 1982 Dec;79(23):7322-5. doi: 10.1073/pnas.79.23.7322.
2
Mobilization of 45Ca from insulin-producing RINm5F cells attached to microcarriers.
Am J Physiol. 1984 Dec;247(6 Pt 1):E719-25. doi: 10.1152/ajpendo.1984.247.6.E719.
3
Correlation between cytosolic free Ca2+ and insulin release in an insulin-secreting cell line.胰岛素分泌细胞系中胞质游离钙离子与胰岛素释放之间的相关性。
J Biol Chem. 1984 Feb 25;259(4):2262-7.
4
Abnormal glucose metabolism accompanies failure of glucose to stimulate insulin release from a rat pancreatic cell line (RINm5F).葡萄糖无法刺激大鼠胰腺细胞系(RINm5F)释放胰岛素,同时伴有葡萄糖代谢异常。
Biochem J. 1983 May 15;212(2):439-43. doi: 10.1042/bj2120439.
5
Reduction of the cytosolic calcium activity in clonal insulin-releasing cells exposed to glucose.暴露于葡萄糖的克隆胰岛素释放细胞中胞质钙活性的降低。
Biosci Rep. 1983 Oct;3(10):939-46. doi: 10.1007/BF01140663.
6
Depolarization-independent net uptake of calcium into clonal insulin-releasing cells exposed to glucose.暴露于葡萄糖的克隆胰岛素释放细胞中,钙的去极化非依赖性净摄取。
Biosci Rep. 1983 Oct;3(10):927-37. doi: 10.1007/BF01140662.
7
Effects of forskolin on insulin release and cyclic AMP content in rat pancreatic islets.福司可林对大鼠胰岛胰岛素释放及环磷酸腺苷含量的影响。
Endocrinology. 1983 Dec;113(6):2311-3. doi: 10.1210/endo-113-6-2311.
8
Insulin, glucagon, and somatostatin receptors on cultured cells and clones from rat islet cell tumor.大鼠胰岛细胞瘤培养细胞及克隆上的胰岛素、胰高血糖素和生长抑素受体
Diabetes. 1982 Jun;31(6 Pt 1):521-31. doi: 10.2337/diab.31.6.521.
9
Forskolin: a unique diterpene activator of cyclic AMP-generating systems.福司可林:一种独特的环磷酸腺苷生成系统二萜激活剂。
J Cyclic Nucleotide Res. 1981;7(4):201-24.
10
Forskolin: unique diterpene activator of adenylate cyclase in membranes and in intact cells.福斯高林:膜及完整细胞中独特的腺苷酸环化酶二萜激活剂。
Proc Natl Acad Sci U S A. 1981 Jun;78(6):3363-7. doi: 10.1073/pnas.78.6.3363.