Failure of high-dose insulin treatment to increase beta-cell insulin content in diabetic non obese diabetic (NOD) mice

Failure of high-dose insulin treatment to increase beta-cell insulin content in diabetic non obese diabetic (NOD) mice
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DOI:
10.1016/s0168-8227(97)00056-9
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发表时间:
1997-07-01
影响因子:
5.1
通讯作者:
Buschard, K
Buschard, K
中科院分区:
医学3区
文献类型:
--
作者:
Bache, I;Jorgensen, KH;Buschard, K

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已发现在胰岛素依赖型糖尿病(IDDM)临床发作后的第一阶段进行高剂量胰岛素治疗可减少人类的糖尿病表现。本研究的目的是检查在该实验性IDDM动物模型中,新诊断的糖尿病非肥胖糖尿病(NOD)小鼠的高剂量胰岛素治疗是否会增加治疗终止后的β细胞胰岛素含量。将新诊断的糖尿病雌性NOD小鼠随机分为三组,包括低剂量胰岛素治疗组(n=10),皮下注射15 IU/kg/天NPH 14天,随后5天不注射胰岛素,高剂量胰岛素治疗组(n = 8)皮下注射150 IU/kg胰岛素,kg/天的Actrapid持续14天,随后5天不使用胰岛素,未治疗组在诊断后3天处死(n = 11)。将年龄匹配的非糖尿病未治疗的雌性NOD小鼠(n = 11)的参照组包括在研究中,并与未治疗的糖尿病小鼠同时处死。通过比较三个糖尿病组(分别由新诊断的未治疗小鼠、低剂量胰岛素治疗小鼠和高剂量胰岛素治疗小鼠组成),未发现从总胰腺提取的胰岛素量的显著差异。该水平比非糖尿病组低约100倍。在整个研究中,两个治疗的糖尿病组中的血糖值处于高水平(中值> 18 mM)。我们的结论是,在新诊断的糖尿病NOD小鼠早期高剂量胰岛素治疗后,β细胞胰岛素含量没有增加,至少在高血糖值的存在下没有。(C)1997 Elsevier Science爱尔兰有限公司
High-dose insulin treatment in the first period after clinical onset of insulin-dependent diabetes mellitus (IDDM) has been found to reduce diabetic manifestations in humans. The aim of the present study was to examine whether high-dose insulin treatment of newly diagnosed diabetic non obese diabetic (NOD) mice would increase beta-cell insulin content after termination of treatment in this experimental IDDM animal model. Newly diagnosed diabetic female NOD mice were randomized into three groups composed of a low-dose insulin treated group (n=10) injected subcutaneously with 15 IU/kg per day of NPH for 14 days followed by 5 days without insulin, a high-dose insulin treated group (n = 8) injected subcutaneously with 150 IU/kg per day of Actrapid for 14 days followed by 5 days without insulin and an untreated group sacrificed 3 days after diagnosis (n = 11). A reference group of age matched non-diabetic untreated female NOD mice (n = 11) was included in the study and sacrificed at the same time as the untreated diabetic mice. No significant difference in the amount of insulin extracted from the total pancreas was found by comparison of the three diabetic groups, consisting of the newly diagnosed untreated mice, the low-dose insulin treated mice and the high-dose insulin treated mice, respectively. The level was about 100-fold less than in the non-diabetic group. Blood glucose values in the two treated diabetic groups were at a high level (median > 18 mM) throughout the study. We conclude that no increase in beta-cell insulin content could be demonstrated in newly diagnosed diabetic NOD mice after early high-dose insulin treatment, at least not in the presence of high blood glucose values. (C) 1997 Elsevier Science Ireland Ltd.