Elucidation of development and improvement of leptin resistance

与单独使用任何一种治疗方法相比，瘦素和埃塞那肽联合使用显著减少了肥胖2型糖尿病小鼠的食物摄入量和体重。此外，瘦素和埃塞那肽联合应用可使血糖水平恢复正常，同时改善胰岛素敏感性，恢复葡萄糖刺激的胰岛素分泌，恢复非脂肪组织中甘油三酯含量，改善血浆胰高血糖素水平，恢复胰腺胰岛素含量，而不是单独使用。配对喂养实验表明，艾塞那肽通过独立的热量限制机制增强瘦素的作用。这些发现表明，通过激发瘦素的作用，瘦素和埃塞那肽联合应用可能是治疗肥胖2型糖尿病的一种有益的治疗方法。

Coadministration of leptin and exenatide significantly reduced food intake and body weight in obese type2 diabetic mice, compared with either monotherapy alone. Moreover, coadministration of leptin and exenatide normalized blood glucose levels accompanied by improvement of insulin sensitivity, restoration of glucose stimulated insulin secretion, normalization of triglyceride contents in non-adipose tissues, improvement of plasma glucagon levels and restoration of pancreatic insulin contents, while not each monotherapy. Pair-feeding experiments indicated that exenatide enhanced the leptin’s effects through independent mechanism of caloric restriction. These findings suggest that coadministration of leptin and exenatide could be a beneficial treatment for obese type2 diabetes by eliciting leptin’s effects.