Rolin Bidda, Deacon Carolyn F, Carr Richard D, Ahrén Bo
Research and Development, Novo Nordisk A/S, Måløv, Denmark.
Eur J Pharmacol. 2004 Jun 28;494(2-3):283-8. doi: 10.1016/j.ejphar.2004.05.013.
Glucagon-like peptide-1 (GLP-1), a future treatment for type 2 diabetes, is efficiently degraded by the enzyme dipeptidyl peptidase IV (DPP IV), yielding the major metabolite GLP-1-(9-36)-amide. In this study, we examined the potential glucose lowering effect of GLP-1-(9-36)-amide in mice and found that GLP-1-(9-36)-amide (3 and 10 nmol/kg) did not affect insulin secretion or glucose elimination when administered intravenously together with glucose (1 g/kg). This was observed both in normal mice and in transgenic mice having a complete disruption of the signalling from the GLP-1 receptor. Furthermore, after blocking insulin secretion, using diazoxide (25 mg/kg), no effect on insulin-independent glucose disposal of GLP-1-(9-36)-amide was observed. Therefore, GLP-1-(9-36)-amide does not affect glucose disposal in mice either in the presence or absence of intact GLP-1-receptors or in the presence or absence of stimulated insulin levels. This suggests that the GLP-1 metabolite is not involved in the regulation of glucose homeostasis.
胰高血糖素样肽-1（GLP-1）是一种未来用于治疗2型糖尿病的药物，它会被二肽基肽酶IV（DPP IV）有效降解，产生主要代谢产物GLP-1-(9-36)-酰胺。在本研究中，我们检测了GLP-1-(9-36)-酰胺对小鼠的潜在降血糖作用，发现当与葡萄糖（1 g/kg）一起静脉注射时，GLP-1-(9-36)-酰胺（3和10 nmol/kg）不影响胰岛素分泌或葡萄糖清除。在正常小鼠和完全破坏GLP-1受体信号传导的转基因小鼠中均观察到这一现象。此外，使用二氮嗪（25 mg/kg）阻断胰岛素分泌后，未观察到GLP-1-(9-36)-酰胺对非胰岛素依赖性葡萄糖处置有影响。因此，无论是否存在完整的GLP-1受体，也无论是否存在刺激的胰岛素水平，GLP-1-(9-36)-酰胺均不影响小鼠的葡萄糖处置。这表明GLP-1代谢产物不参与葡萄糖稳态的调节。
