Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
Diabetes Obes Metab. 2009 Sep;11(9):884-90. doi: 10.1111/j.1463-1326.2009.01066.x. Epub 2009 Jun 5.
The glucagon-like peptide-1 (GLP-1) receptor agonist, exendin-4, has previously been shown to delay the onset of diabetes when administered to Goto-Kakizaki (GK) rats in the prediabetic period. The present study aimed to evaluate whether long-term administration of exendin-4 to GK rats in the diabetic period would improve their diabetes and how glycaemic control was affected following drug wash-out.
Glycaemic control was assessed in diabetic GK rats during 12 weeks of exendin-4 or vehicle treatment. Moreover, some animals were followed for an additional 9 weeks without treatment.
Glycaemic control was seen to deteriorate in vehicle-treated animals, as assessed by increased glycated haemoglobin A1c (HbA1c), whereas HbA1c improved in exendin-4-treated animals. Following an additional 9 weeks without treatment, glycaemic control in exendin-4-treated animals remained below baseline value and thus remained significantly lower than that of vehicle-treated animals. Following exendin-4 administration, oral glucose tolerance tests revealed greatly reduced glucose and insulin excursions compared with vehicle-treated animals, whereas following overnight drug wash-out, only little difference was seen, suggesting that the improvement in glycaemic control may have been obtained primarily by increased postprandial control. No significant differences were observed in pancreatic islet morphology or islet hormone content.
Exendin-4 treatment improved glycaemic control in diabetic GK rats, independent of changes in beta-cell mass. Additionally, progression of the disease seemed to be delayed because the improvement in HbA1c was still apparent 9 weeks after cessation of treatment.
胰高血糖素样肽-1（GLP-1）受体激动剂 exendin-4 曾被证明可在糖尿病前期的 Goto-Kakizaki（GK）大鼠中延迟糖尿病的发作。本研究旨在评估在糖尿病期给予 GK 大鼠长期 exendin-4 治疗是否会改善其糖尿病，以及在停药后血糖控制会受到怎样的影响。
在 exendin-4 或载体治疗的 12 周期间评估糖尿病 GK 大鼠的血糖控制情况。此外，一些动物在没有治疗的情况下再随访 9 周。
通过糖化血红蛋白 A1c（HbA1c）的增加，发现载体处理的动物的血糖控制恶化，而 exendin-4 处理的动物的 HbA1c 得到改善。在没有治疗的另外 9 周后，exendin-4 治疗的动物的血糖控制仍低于基线值，因此仍明显低于载体处理的动物。在给予 exendin-4 后，口服葡萄糖耐量试验显示与载体处理的动物相比，葡萄糖和胰岛素的波动大大降低，而在过夜药物洗脱后，仅观察到微小差异，表明血糖控制的改善可能主要通过增加餐后控制获得。胰腺胰岛形态或胰岛激素含量无显著差异。
exendin-4 治疗改善了糖尿病 GK 大鼠的血糖控制，与β细胞质量的变化无关。此外，由于停药 9 周后 HbA1c 的改善仍然明显，疾病的进展似乎被延迟。
