Thulesen J, Orskov C, Holst J J, Poulsen S S
University of Copenhagen, Panum Institute, Denmark.
Endocrinology. 1997 Jan;138(1):62-8. doi: 10.1210/endo.138.1.4827.
Streptozotocin, which induces diabetes mellitus in experimental animals, has been reported to be taken up by beta-cells by means of the glucose transporter 2 (GLUT2) and then reduce the cellular level of NAD+, leading to necrosis of the beta-cells. We investigated the effect of insulin pretreatment on the diabetogenic action of streptozotocin (60 mg/kg). Four groups of rats were studied: 1) a group that received streptozotocin (STZ), 2) a group that received insulin pretreatment and streptozotocin (INS + STZ), 3) a group that received insulin (INS), and 4) a control group (CTRL). Insulin treatment reduced the beta-cell immunoreactivity (IR) of insulin and GLUT2, which, thus, was reduced in INS + STZ rats at the time of streptozotocin injection. In STZ rats, plasma insulin concentrations after 3 weeks as well as insulin concentrations in pancreatic tissue samples were significantly lower than those in CTRL rats [plasma, 274.3 +/- 101.9 vs. 1078.8 +/- 254.9 pmol/liter (P < 0.05); tissue, 0.46 +/- 0.02 vs. 117.0 +/- 28.4 nmol/g (P < 0.01)]. INS + STZ rats did not become hyperglycemic, and the plasma and tissue levels of insulin were higher than those in STZ rats [plasma, 538.3 +/- 80.1 vs. 274.3 +/- 101.9 pmol/liter (P = 0.08); tissue, 0.46 +/- 0.02 vs. 37.90 +/- 2.13 nmol/g (P < 0.05)]. The immunohistochemical findings of insulin IR in the pancreatic tissues were in accordance with the results obtained by RIA. We conclude that exogenous insulin suppresses the expression of GLUT2 and insulin in beta-cells, and this may prevent the diabetogenic effect of streptozotocin.
链脲佐菌素可在实验动物中诱发糖尿病，据报道它通过葡萄糖转运蛋白2（GLUT2）被β细胞摄取，然后降低细胞内烟酰胺腺嘌呤二核苷酸（NAD +）水平，导致β细胞坏死。我们研究了胰岛素预处理对链脲佐菌素（60 mg/kg）致糖尿病作用的影响。研究了四组大鼠：1）接受链脲佐菌素（STZ）的组，2）接受胰岛素预处理和链脲佐菌素的组（INS + STZ），3）接受胰岛素的组（INS），以及4）对照组（CTRL）。胰岛素治疗降低了胰岛素和GLUT2的β细胞免疫反应性（IR），因此，在注射链脲佐菌素时，INS + STZ大鼠的IR降低。在STZ大鼠中，3周后的血浆胰岛素浓度以及胰腺组织样本中的胰岛素浓度显著低于CTRL大鼠[血浆，274.3±101.9 vs. 1078.8±254.9 pmol/升（P <0.05）；组织，0.46±0.02 vs. 117.0±28.4 nmol/克（P <0.01）]。INS + STZ大鼠未出现高血糖，且血浆和组织胰岛素水平高于STZ大鼠[血浆，538.3±80.1 vs. 274.3±101.9 pmol/升（P = 0.08）；组织，0.46±0.02 vs. 37.90±2.13 nmol/克（P <0.05）]。胰腺组织中胰岛素IR的免疫组织化学结果与放射免疫分析结果一致。我们得出结论，外源性胰岛素抑制β细胞中GLUT2和胰岛素的表达，这可能会预防链脲佐菌素的致糖尿病作用。
