Protective effect of recombinant human glucagon-like peptide-1 (rhGLP-1) pretreatment in STZ-induced diabetic mice

Human glucagon-like peptide-1 (hGLP-1) and its mimetics have emerged as therapies for type 2 diabetes. However, clinical treatment of diabetes with hGLP-1 is ineffective because of rapid DPPIV-mediated hGLP-1 degradation in the circulation. In this study, we investigated the protective effect of recombinant human glucagon-like peptide-1 (rhGLP-1) treatment on STZ-induced diabeticmice. Mice were treated daily with rhGLP-1 (24 nmol/kg body weight) starting before or after STZ injection (40mg/kg body weight) to induce diabetes. Mice pretreated with rhGLP-1 before but not after STZ showed significantly reduced blood glucose levels (P < 0.05), increased oral glucose tolerance (area under the curve, 1740 +/- 71.18 vs 2416 +/- 205.6, P < 0.05). Furthermore, the bioproduct of lipid peroxidation, MDA, was reduced and SOD and GSH-PX activities were enhanced globally and in pancreas of mice that received rhGLP-1 pretreatment before STZ, when comparing with STZ-treated mice. Finally, STZ-induced pancreatic islet damage was rescued by rhGLP-1 pretreatment. Taken together, the results of this study demonstrate that rhGLP-1 pretreatment has a protective effect against STZ-induced diabetes in mice. These findings suggest that the GLP-1 pretreatment may be a new therapeutic strategy in the preventive and protective treatment during diabetes initiation and progression. Copyright (C) 2011 European Peptide Society and John Wiley & Sons, Ltd.