Retinoic acid receptor transcripts and effects of retinol and retinoic acid on glucagon secretion from rat islets and glucagon-secreting cell lines
Retinoic acid receptor transcripts and effects of retinol and retinoic acid on glucagon secretion from rat islets and glucagon-secreting cell lines
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DOI：
10.1016/s0026-0495(96)90282-6
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发表时间：
1996-03-01
影响因子：
9.8
通讯作者：
Matthews, KA
中科院分区：
文献类型：
--
作者：
Chertow, BS;Driscoll, HK;Matthews, KA
采用完整的大鼠胰岛、仓鼠In-R1-G9细胞和小鼠α TC-1克隆9转基因肿瘤胰高血糖素分泌细胞，研究视黄醇（ROH）和视黄酸（RA）对胰高血糖素分泌的影响。由于维生素A的作用可能通过核RA受体（RARs）和细胞质ROH-和RA-结合蛋白（CRBP和CRABP）介导，因此还通过Northern blot分析细胞中RARs、CRBP和CRABP mRNA的表达。在2.8 mmol/L葡萄糖和维生素a缺乏（A-def）培养基或不同浓度的ROH和RA培养基中培养胰岛和细胞。使用完整的胰岛，RA 10和100 nmol/L抑制胰高血糖素分泌约为对照水平的60%。在In-R1-G9细胞中，ROH 0.175 ~ 5.0 μ mol/L对胰高血糖素分泌的抑制作用为对照的60% ~ 83%，RA 100和1000 nmol/L对胰高血糖素分泌的抑制作用为对照的72% ~ 43%。使用α TC-1细胞。1.75 μ mol/L的ROH抑制胰高血糖素分泌量为对照的80%，RA 1 ~ 100 nmol/L抑制胰高血糖素分泌量为对照的83% ~ 68%。分泌抑制呈剂量依赖性。在α TC-1和in - r1 - g9总RNA提取物中检测到RAR α RNA转录物；在α TC-1细胞中检测到RAR γ转录本。我们得出以下结论：(1)ROH和RA对培养的大鼠胰岛和分泌胰高血糖素的细胞系的胰高血糖素分泌有抑制作用，且在细胞系中RA的作用呈剂量依赖性；(2)在摩尔基础上，RA的效力是ROH的10- 100倍，这一发现与RA在ct细胞水平上是ROH的活性代谢物相一致；(3)这种抑制可能通过类视黄醇作用的经典途径介导，涉及核RARs和特定蛋白的基因表达。版权所有(C) 1996年由W.B.桑德斯公司
Using intact rat islets, hamster In-R1-G9 cells, and mouse alpha TC-1 clone 9 transgenic tumoral glucagon-secreting cells, we determined the effects of retinol (ROH) and retinoic acid (RA) on glucagon secretion. Since vitamin A effects may be mediated through nuclear RA receptors (RARs) and cytoplasmic ROH- and RA-binding proteins (CRBP and CRABP), cells were also assayed for RARs, CRBP, and CRABP mRNA by Northern blot analyses. Islets and cells were cultured in 2.8 mmol/L glucose and vitamin A-deficient (A-def) medium or in different concentrations of ROH and RA. Using intact islets, RA 10 and 100 nmol/L inhibited glucagon secretion to approximately 60% of control levels. Using In-R1-G9 cells, ROH 0.175 to 5.0 mu mol/L inhibited glucagon secretion to 60% to 83% of control levels, and RA 100 and 1,000 nmol/L inhibited glucagon secretion from 72% to 43% of control levels, respectively. Using alpha TC-1 cells. ROH 1.75 mu mol/L inhibited glucagon secretion to 80% of control levels, and RA 1 to 100 nmol/L inhibited secretion from 83% to 68% of control levels. Inhibition of secretion was dose-dependent. RAR alpha RNA transcripts were detected in alpha TC-1 and In-R1-G9 total RNA extracts; RAR gamma transcripts were detected in alpha TC-1 cells. We conclude the following: (1) ROH and RA inhibit glucagon secretion in cultured rat islets and glucagon-secreting cell lines, and in cell lines the effect of RA is dose-dependent; (2) on a molar basis, RA is on the order of 10- to 100-fold more potent than ROH, a finding consistent with RA being the active metabolite of ROH at the ct-cell level; and (3) this inhibition may be mediated through classic pathways of retinoid action involving nuclear RARs and gene expression of specific proteins. Copyright (C) 1996 by W.B. Saunders Company