Wolffenbuttel B H, Vreeburg J
Department of Internal Medicine III, University Hospital, Maastricht, The Netherlands.
Diabetes Res. 1988 Oct;9(2):77-9.
In recent years it was suggested that in type 2 diabetes mellitus glucose exerts a direct toxic effect: the hyperglycaemic state itself could contribute to the defects in insulin secretion. We studied the effects of insulin treatment on pancreatic insulin content in neonatal Wistar rats made hyperglycaemic with streptozotocin (SZ, 90 mg/kg, injected intraperitoneally at two days of age). Our hypothesis was that normoglycaemia effected by insulin treatment could diminish the beta-cell damage in these animals. Insulin-treated animals received Lente MC insulin (8 mU/g body weight/day) during the first six days after SZ-injection. At four days of age, blood glucose levels (BG) in the fed state were 5.9 +/- 1.0 mmol/l in control animals (n = 14), whereas all untreated SZ-animals (n = 10) showed BG above 11 mmol/l (mean 15.9 +/- 3.4 mmol/l). In all 11 insulin-treated SZ-animals BG was below 10 mmol/l (mean 4.3 +/- 2.7 mmol/l). At 10 days of age plasma insulin levels did not differ between the three groups. However, pancreatic insulin content was 114 +/- 37 ng/mg tissue in the insulin-treated, and 93 +/- 34 ng/mg tissue (p = ns) in the untreated SZ-animals, compared to 516 +/- 257 ng/mg tissue in the controls (p less than 0.001). BG at four days and the pancreatic insulin contents at 10 days were not correlated. We conclude that intraperitoneal streptozotocin injection in neonatal rats produced marked hyperglycaemia and reduction of pancreatic insulin content. Insulin treatment did not result in improved recovery of the insulin stores in the pancreas. Thus, the additive toxic effect of hyperglycaemia on the beta-cells could not be demonstrated.
近年来，有人提出在2型糖尿病中葡萄糖具有直接毒性作用：高血糖状态本身可能导致胰岛素分泌缺陷。我们研究了胰岛素治疗对新生Wistar大鼠胰腺胰岛素含量的影响，这些大鼠在出生两天时腹腔注射链脲佐菌素（SZ，90mg/kg）造成高血糖。我们的假设是胰岛素治疗使血糖正常化可减少这些动物的β细胞损伤。胰岛素治疗组动物在注射链脲佐菌素后的头六天接受慢胰岛素锌悬液（8mU/g体重/天）。4日龄时，对照组动物（n = 14）喂食状态下的血糖水平（BG）为5.9±1.0mmol/L，而所有未治疗的链脲佐菌素处理动物（n = 10）的血糖水平均高于11mmol/L（平均15.9±3.4mmol/L）。在所有11只胰岛素治疗的链脲佐菌素处理动物中，血糖水平低于10mmol/L（平均4.3±2.7mmol/L）。10日龄时，三组动物的血浆胰岛素水平无差异。然而，胰岛素治疗组胰腺胰岛素含量为114±37ng/mg组织，未治疗的链脲佐菌素处理动物为93±34ng/mg组织（p =无显著差异），而对照组为516±257ng/mg组织（p＜0.001）。4日龄时的血糖水平与10日龄时的胰腺胰岛素含量无相关性。我们得出结论，新生大鼠腹腔注射链脲佐菌素可导致明显的高血糖和胰腺胰岛素含量降低。胰岛素治疗并未使胰腺胰岛素储备的恢复得到改善。因此，未能证明高血糖对β细胞的叠加毒性作用。
