Linn T, Schneider K, Göke B, Federlin K
Medical Clinic III and Polyclinic, Justus Liebig University, Giessen, Germany.
Acta Diabetol. 1996 Mar;33(1):19-24. doi: 10.1007/BF00571935.
The effect of the insulinotropic gut hormone glucagon-like-peptide-1 (GLP-1) was studied on the residual insulin capacity of prediabetic nonobese diabetic (NOD) mice, a model of insulin-dependent diabetes mellitus (type 1). This was done using isolated pancreas perfusion and dynamic islet perifusion. Prediabetes was defined by insulitis and fasting normoglycemia. Insulitis occurred in 100% of NOD mice beyond the age of 12 weeks. K values in the intravenous glucose tolerance test were reduced in 20-week-old NOD mice compared with age matched non-diabetes-prone NOR (nonobese resistant) mice (2.4 +/- 1.1 vs 3.8 +/- 1.5% min-1, P < 0.05). Prediabetic NOD pancreases were characterized by a complete loss of the glucose-induced first-phase insulin release. In perifused NOD islets GLP-1, at concentrations already effective in normal islets, left the insulin release unaltered. However, a significant rise of glucose-dependent insulin secretion occurred for GLP-1 concentrations > 0.1 nM. This was obtained with both techniques, dynamic islet perifusion and isolated pancreas perfusion, indicating a direct effect of GLP-1 on the beta-cell. Analysis of glucose-insulin dose-response curves revealed a marked improvement of glucose sensitivity of the NOD endocrine pancreas in the presence of GLP-1 (half-maximal insulin output without GLP-1 15.2 mM and with GLP-1 9.4 mM, P < 0.002). We conclude that GLP-1 can successfully reverse the glucose sensing defect of islets affected by insulitis.
研究了促胰岛素肠道激素胰高血糖素样肽-1（GLP-1）对胰岛素依赖型糖尿病（1型）的糖尿病前期非肥胖糖尿病（NOD）小鼠残余胰岛素分泌能力的影响。采用离体胰腺灌注和动态胰岛灌流技术进行研究。糖尿病前期通过胰岛炎和空腹血糖正常来定义。12周龄以上的NOD小鼠100%发生胰岛炎。与年龄匹配的非糖尿病易感性NOR（非肥胖抗性）小鼠相比，20周龄NOD小鼠静脉葡萄糖耐量试验中的K值降低（2.4±1.1对3.8±1.5%min-1，P<0.05）。糖尿病前期NOD胰腺的特征是葡萄糖诱导的第一相胰岛素释放完全丧失。在灌流的NOD胰岛中，GLP-1在对正常胰岛已经有效的浓度下，胰岛素释放未改变。然而，对于GLP-1浓度>0.1 nM，葡萄糖依赖性胰岛素分泌显著增加。动态胰岛灌流和离体胰腺灌注这两种技术均得到此结果，表明GLP-1对β细胞有直接作用。葡萄糖-胰岛素剂量反应曲线分析显示，在存在GLP-1的情况下，NOD内分泌胰腺的葡萄糖敏感性显著改善（无GLP-1时胰岛素输出的半数最大值为15.2 mM，有GLP-1时为9.4 mM，P<0.002）。我们得出结论，GLP-1可以成功逆转受胰岛炎影响的胰岛的葡萄糖感知缺陷。
