Koranyi L, Bourey R, Turk J, Mueckler M, Permutt M A
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri.
Diabetologia. 1992 Dec;35(12):1125-32. doi: 10.1007/BF00401365.
The question posed by these studies was whether chronic adaptive changes in glucose-stimulated insulin secretion are accompanied by comparable changes in islet Beta-cell glucose transporter (GLUT 2) gene expression. Control, fasted (3-day), insulin-injected hypoglycaemic (5-day), and dexamethasone-treated (4-day) rats (n = 5 for each condition), were studied. After fasting significant decrements in proinsulin mRNA/microgram RNA (-32%, p < 0.05) and islet amyloid polypeptide mRNA/microgram RNA (-44%, p < 0.05) were observed, while there was no change in GLUT 2 mRNA/microgram RNA (-13%, p > 0.05). After insulin-induced hypoglycaemia, decrements in proinsulin mRNA/microgram RNA (-49%, p < 0.01) and islet amyloid polypeptide mRNA/microgram RNA (-44%, p < 0.01) were also observed, with no change in islet GLUT 2 mRNA/microgram RNA (-18%, p > 0.05). Dexamethasone treatment resulted in a marked stimulatory effect on proinsulin mRNA/microgram RNA (+236%, p < 0.001) and islet amyloid polypeptide mRNA/microgram RNA (+221%, p < 0.01), while again there was no change in islet GLUT 2 mRNA/microgram RNA (+0.3%, p > 0.05). Quantitative immunoblot analysis with a GLUT 2 specific antibody revealed no change in islet GLUT 2 protein with fasting, but a small decrease (-39 +/- 11%) in islet GLUT 2/microgram protein after insulin-induced hypoglycaemia. These results do not support the hypothesis that chronic changes in glucose-stimulated insulin secretion are accompanied by changes in GLUT 2 expression. In contrast to the lack of correlation with GLUT 2, there was a striking correlation between proinsulin and islet amyloid polypeptide mRNAs for all experimental conditions (r = 0.974, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
这些研究提出的问题是，葡萄糖刺激的胰岛素分泌的慢性适应性变化是否伴随着胰岛β细胞葡萄糖转运体（GLUT 2）基因表达的相应变化。对对照组、禁食（3天）、注射胰岛素致低血糖（5天）以及地塞米松处理（4天）的大鼠（每种情况n = 5）进行了研究。禁食后，观察到胰岛素原mRNA/微克RNA显著下降（-32%，p < 0.05）以及胰岛淀粉样多肽mRNA/微克RNA显著下降（-44%，p < 0.05），而GLUT 2 mRNA/微克RNA没有变化（-13%，p > 0.05）。胰岛素诱导低血糖后，胰岛素原mRNA/微克RNA（-49%，p < 0.01）和胰岛淀粉样多肽mRNA/微克RNA（-44%，p < 0.01）也出现下降，胰岛GLUT 2 mRNA/微克RNA没有变化（-18%，p > 0.05）。地塞米松处理对胰岛素原mRNA/微克RNA（+236%，p < 0.001）和胰岛淀粉样多肽mRNA/微克RNA（+221%，p < 0.01）产生显著刺激作用，而胰岛GLUT 2 mRNA/微克RNA同样没有变化（+0.3%，p > 0.05）。用GLUT 2特异性抗体进行的定量免疫印迹分析显示，禁食时胰岛GLUT 2蛋白没有变化，但胰岛素诱导低血糖后，胰岛GLUT 2/微克蛋白略有下降（-39 +/- 11%）。这些结果不支持葡萄糖刺激的胰岛素分泌的慢性变化伴随着GLUT 2表达变化这一假说。与缺乏与GLUT 2的相关性相反，在所有实验条件下，胰岛素原和胰岛淀粉样多肽mRNA之间存在显著相关性（r = 0.974，p < 0.001）。（摘要截短至250字）
