GLUCOSE TRANSPORTER GENE EXPRESSION IN RAT BRAIN PRETRANSLATIONAL CHANGES ASSOCIATED WITH CHRONIC INSULIN-INDUCED HYPOGLYCEMIA FASTING AND DIABETES

GLUCOSE TRANSPORTER GENE EXPRESSION IN RAT BRAIN PRETRANSLATIONAL CHANGES ASSOCIATED WITH CHRONIC INSULIN-INDUCED HYPOGLYCEMIA FASTING AND DIABETES
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DOI:
10.1016/1044-7431(91)90051-o
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发表时间:
1991-01-01
影响因子:
3.5
通讯作者:
PERMUTT A M A
PERMUTT A M A
中科院分区:
医学3区
文献类型:
--
作者:
KORANYI L;BOUREY R E;PERMUTT A M A

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在引起成年大鼠血浆葡萄糖和胰岛素慢性变化的三种条件下评估大脑主要葡萄糖转运蛋白基因 (GLUT-1) 的稳态水平:(i) 重复注射胰岛素 5 天,导致血浆葡萄糖水平至少 3 天为 60-70 mg/dl; (ii) 禁食3天; (iii) 持续 1 周的中度链脲佐菌素诱发的糖尿病。通过使用 HepG2/红细胞 (GLUT-1) [32P]cRNA 探针进行点印迹杂交来测量脑 GLUT-1 mRNA,并通过使用多克隆抗体 (R493) 进行免疫印迹分析来测量 GLUT-1 蛋白。注射胰岛素导致低血糖,GLUT-1 mRNA增加(143.+-.15%,P<0.05),GLUT-1蛋白增加(141.+-.6%,P<0.05)。 GLUT-1 mRNA 的增加是大脑特有的,而肝脏或肾脏中没有观察到变化。禁食导致中度低血糖、血浆胰岛素降低、GLUT-1 mRNA 增加(131 .+-. 17%,与对照相比,P < 0.05),而 GLUT-1 蛋白没有变化(125 .+-. 9%,N.S.)。轻度链脲佐菌素糖尿病导致高血糖、血浆胰岛素检测不到、GLUT-1 mRNA 减少(65 .+-. 6%,与对照相比,P < 0.05),而 GLUT-1 蛋白无变化(84 .+-. 9%,N.S.)。在三个实验组和对照动物中观察到脑中 GLUT-1 mRNA 水平与血浆葡萄糖浓度之间呈负相关(r = -0.61,P < .0001),这表明血浆葡萄糖浓度可能是大鼠脑中 GLUT-1 水平的至少一个决定因素。这些结果的重要性在于发现大鼠大脑中的 GLUT-1 基因表达在体内受到动物营养和内分泌状态的调节。
Steady-state levels of the major glucose transporter gene (GLUT-1) of the brain were evaluated under three conditions that induced chronic changes in plasma glucose and insulin in adult rats: (i) repeated injection of insulin for 5 days, resulting in plasma glucose levels of 60-70 mg/dl for at least 3 days; (ii) fasting for 3 days; and (iii) moderate streptozotocin-induced diabetes of 1 week duration. Brain GLUT-1 mRNA was measured by dot blot hybridization with a HepG2/erythrocyte (GLUT-1) [32P]cRNA probe, and GLUT-1 protein by immunoblot analysis with a polyclonal antibody (R493). Insulin injection resulted in hypoglycemia, increased GLUT-1 mRNA (143 .+-. 15%, P < 0.05), and increased GLUT-1 protein (141 .+-. 6%, P < 0.05). The increase in GLUT-1 mRNA was specific for brain, as no change was observed in liver or kidney. Fasting resulted in mid hypoglycemia, lower plasma insulin, increased GLUT-1 mRNA (131 .+-. 17%, P < 0.05 vs control), and no change in GLUT-1 protein (125 .+-. 9%, N.S.). Mild streptozotocin diabetes resulted in hyperglycemia, undetectable plasma insulin, decreased GLUT-1 mRNA (65 .+-. 6%, P < 0.05 vs control), and no change in GLUT-1 protein (84 .+-. 9%, N.S.). A negative correlation (r = -0.61, P < .0001) between GLUT-1 mRNA levels in brain and plasma glucose concentrations was observed among the three experimental groups and control animals, suggesting that the plasma glucose concentration may be at least one determinant of GLUT-1 levels in rat brain. The importance of these results is the finding that GLUT-1 gene expression in rat brain is regulation in vivo by the nutritional and endocrine status of the animal.