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

• Published in: Journal of peptide science 2011-07, Vol.17 (7), p.499-504
• Main Authors: Wu, Ye-Lin, Huang, Jing, Liu, Jian, Jin, Ming-Fei, Gu, Mei, Hong, Yiguo, Wu, Zi-Rong
• Format: Article
• Language: English
• Subjects: Animals; Blood; Blood Glucose - metabolism; Body weight; Diabetes mellitus; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - physiopathology; GLP-1; Glucagon-like peptide 1; Glucagon-Like Peptide 1 - genetics; Glucagon-Like Peptide 1 - metabolism; Glucose tolerance; Glucose Tolerance Test; Humans; Islets of Langerhans; Lipid peroxidation; Mice; Oxidative Stress; Pancreas; Pancreas - cytology; Pancreas - pathology; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Recombinant Proteins - therapeutic use; streptozotocin; Superoxide dismutase; type 2 diabetes
• ISSN: 1075-2617; 1099-1387; 1099-1387
• DOI: 10.1002/psc.1352

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 diabetic mice. Mice were treated daily with rhGLP‐1 (24 nmol/kg body weight) starting before or after STZ injection (40 mg/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 © 2011 European Peptide Society and John Wiley & Sons, Ltd. In this paper, we found rhGLP‐1 pretreatment has a protective effect against STZ‐induced diabetes in mice. Pretratment of rhGLP‐1 not only decreased blood glucose and improved glucose tolerance but also significantly reduced the level of oxidative stress and elevated the antioxidant defense system activities in STZ‐induced diabetic mouse model. These findings suggest that GLP‐1 and its analogs may be a new therapeutic strategy in the preventive and protective treatment of diabetes mellitus.