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细胞内pH值是营养物质刺激胰岛时的一个偶联因子吗?

Is intracellular pH a coupling factor in nutrient-stimulated pancreatic islets?

作者信息

Best L, Bone E A, Meats J E, Tomlinson S

机构信息

Department of Medicine, University of Manchester Medical School.

出版信息

J Mol Endocrinol. 1988 Jul;1(1):33-8. doi: 10.1677/jme.0.0010033.

DOI:10.1677/jme.0.0010033
PMID:3076778
Abstract

Intracellular pH (pHi) was monitored in dispersed pancreatic islet cells from rats using the fluorescent dye 2'7'bis-carboxyethyl-5'(6')-carboxyfluorescein. The addition of a weak acid (acetate, propionate or formate) provoked a rapid fall in pHi, corresponding to approximately 0.2 units, following by a slower return to the basal value. Amiloride also caused a rapid fall in pHi, but no recovery occurred in this case. Addition of NH4Cl induced a rise in pHi. Of the nutrients tested, only glyceraldehyde produced a fall in pHi, both glucose and alpha-ketoisocaproate causing a gradual and sustained rise in pHi. Insulin secretion and inositol lipid metabolism in response to nutrient stimuli were markedly inhibited by NH4Cl. The responses to non-nutrient stimuli were unaffected. Glucose-induced insulin secretion and inositol lipid metabolism were potentiated in the presence of amiloride. No such potentiation, however, was observed in the presence of weak acids. Amiloride and weak acids shared the ability to reduce the fractional outflow rate of 45Ca2+. It is concluded that pharmacological manipulations of pHi can influence certain aspects of islet cell function, such as calcium handling, though it seems unlikely that the stimulation of islets by nutrient secretagogues occurs as a result of changes in pHi.

摘要

使用荧光染料2'7'-双羧乙基-5'(6')-羧基荧光素监测大鼠分散胰岛细胞内的pH值(细胞内pH,pHi)。加入弱酸(乙酸、丙酸或甲酸)会使pHi迅速下降约0.2个单位,随后缓慢恢复至基础值。氨氯吡咪也会使pHi迅速下降,但在这种情况下不会恢复。加入氯化铵会使pHi升高。在所测试的营养物质中,只有甘油醛会使pHi下降,葡萄糖和α-酮异己酸都会使pHi逐渐持续升高。氯化铵显著抑制了营养刺激引起的胰岛素分泌和肌醇脂质代谢。对非营养刺激的反应不受影响。在氨氯吡咪存在的情况下,葡萄糖诱导的胰岛素分泌和肌醇脂质代谢增强。然而,在弱酸存在的情况下未观察到这种增强作用。氨氯吡咪和弱酸都具有降低45Ca2+分数流出率的能力。得出的结论是,对pHi的药理学操作可以影响胰岛细胞功能的某些方面,如钙处理,尽管营养促分泌剂对胰岛的刺激似乎不太可能是由pHi的变化引起的。

相似文献

1
Is intracellular pH a coupling factor in nutrient-stimulated pancreatic islets?细胞内pH值是营养物质刺激胰岛时的一个偶联因子吗?
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Am J Physiol. 1983 Jan;244(1):E3-18. doi: 10.1152/ajpendo.1983.244.1.E3.

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Dimethyl amiloride improves glucose homeostasis in mouse models of type 2 diabetes.二甲基氨氯吡脒可改善2型糖尿病小鼠模型的葡萄糖稳态。
Am J Physiol Endocrinol Metab. 2008 Jun;294(6):E1097-108. doi: 10.1152/ajpendo.00748.2007. Epub 2008 Apr 15.
3
Amiloride derivatives enhance insulin release in pancreatic islets from diabetic mice.氨氯地平衍生物可增强糖尿病小鼠胰岛中的胰岛素释放。
BMC Endocr Disord. 2005 Dec 8;5:9. doi: 10.1186/1472-6823-5-9.
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Nutrient-stimulated insulin secretion in mouse islets is critically dependent on intracellular pH.小鼠胰岛中营养物质刺激的胰岛素分泌严重依赖于细胞内pH值。
BMC Endocr Disord. 2004 Jun 11;4(1):1. doi: 10.1186/1472-6823-4-1.
5
Effects of lactate on pancreatic islets. Lactate efflux as a possible determinant of islet-cell depolarization by glucose.乳酸对胰岛的影响。乳酸外流作为葡萄糖导致胰岛细胞去极化的一个可能决定因素。
Biochem J. 1989 Apr 15;259(2):507-11. doi: 10.1042/bj2590507.
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Intracellular pH and the stimulus-secretion coupling in insulin-producing RINm5F cells.胰岛素分泌细胞RINm5F中的细胞内pH值与刺激-分泌偶联
Biochem J. 1992 Oct 1;287 ( Pt 1)(Pt 1):59-66. doi: 10.1042/bj2870059.