ZRC communication no. 291.
Omeprazole improves the anti-obesity and antidiabetic effects of exendin-4 in db/db mice (奥美拉唑改善唾液素-4 对db/db小鼠的减肥与降糖作用)*
Version of Record online: 26 APR 2013
© 2012 Wiley Publishing Asia Pty Ltd and Ruijin Hospital, Shanghai Jiaotong University School of Medicine
Journal of Diabetes
Volume 5, Issue 2, pages 163–171, June 2013
How to Cite
Patel, V., Joharapurkar, A., Gandhi, T., Patel, K., Dhanesha, N., Kshirsagar, S., Dhote, V., Detroja, J., Bahekar, R. and Jain, M. (2013), Omeprazole improves the anti-obesity and antidiabetic effects of exendin-4 in db/db mice (奥美拉唑改善唾液素-4 对db/db小鼠的减肥与降糖作用). Journal of Diabetes, 5: 163–171. doi: 10.1111/j.1753-0407.2012.00227.x
- Issue online: 26 APR 2013
- Version of Record online: 26 APR 2013
- Accepted manuscript online: 25 JUL 2012 10:41AM EST
- Received 9 May 2012; revised 19 June 2012; accepted 16 July 2012.
Background: In addition to its glucoregulatory actions, exendin-4, a stable glucagon-like peptide-1 receptor agonist, exhibits protective effects in the pancreas and anti-obesity effects. Suitable combination treatment with other anti-obesity or pancreas protective agents would be an effective approach to optimize these additional effects. In the present study, we investigated the effects of the addition of omeprazole, a proton pump inhibitor, to exendin-4 in db/db mice, an experimental model of obesity and type 2 diabetes.
Methods: The effects repeated dose treatment for 14 days with exendin-4 (8 μg/kg, s.c.) and omeprazole (30 mg/kg, s.c.) on glycemic control, food intake, and body weight were determined in obese and hyperglycemic db/db mice. The effects of these treatments on plasma gastrin, ghrelin, and leptin levels were determined, along with effects on nausea-like symptoms. The pancreatic effects of the repeated dose treatment were assessed by measuring %HbA1c in the circulation as well as pancreatic insulin and glucagon content and glucokinase activity.
Results: Combination treatment resulted in significant decreases in plasma leptin and ghrelin levels after repeated dosing. Omeprazole improved the anorectic and body weight-lowering effects and reversed the inhibitory effect of exendin-4 on gastrin levels after repeated dose treatment. The 14-day combination treatment significantly reduced glucose excursion and improved insulin levels, with a concomitant decrease in %HbA1c levels. It also improved glucokinase activity and pancreatic insulin content, with a significant decrease in glucagon content.
Conclusions: Combined treatment with omeprazole with exendin-4 reduces food intake and body weight gain, most likely through changes in plasma ghrelin and leptin levels, and improves pancreatic insulin and glucagon content by improving glucokinase activity.
方法： 在肥胖的高血糖db/db小鼠中使用唾液素-4（8 μg/kg，皮下注射）与奥美拉唑（30 mg/kg，皮下注射）重复治疗14天后测定其对血糖控制、食物摄入以及体重的影响。测定该治疗对血浆胃泌素、胃促生长素以及瘦素水平的影响，以及它们对恶心样症状的影响。通过测定循环中的%HbA1c、胰腺内的胰岛素与胰升糖素含量以及葡萄糖激酶活性来评估重复治疗对胰腺的影响。