Duodenal-Jejunal Bypass Surgery Reverses Diabetic Phenotype and Reduces Obesity in db/db Mice.

Yongjun Liang, Yueqian Wang, Zhengdong Qiao, Ting Cao, Ying Feng, Lin Zhang, Peng Zhang
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Abstract

Type 2 diabetes mellitus (T2DM), a complex metabolic disorder typically accompanying weight gain, is associated with progressive β-cell failure and insulin resistance. Bariatric surgery ameliorates glucose tolerance and provides a near-perfect treatment. Duodenal-jejunal bypass (DJB) is an experimental procedure and has been studied in several rat models, but its influence in db/db mice, a transgenic model of T2DM, remains unclear. To investigate the effectiveness of DJB in db/db mice, we performed the surgery and evaluated metabolism improvement. Results showed that mice in DJB group weighed remarkably less than sham group two weeks after surgery. Compared to the preoperative level, postoperative fasting blood glucose (FBG) was dramatically reduced. Statistical analysis revealed that changes in body weight and FBG were significantly correlated. Besides, DJB surgery altered plasma insulin level with approximate 40% reduction. Thus, for the first time we proved that DJB can achieve rapid therapeutic effect in transgenic db/db mice with severe T2DM as well as obesity. In addition, decreased insulin level reflected better insulin sensitivity induced by DJB. In conclusion, our study demonstrates that DJB surgery may be a potentially effective way to treat obesity-associated T2DM.

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十二指肠-空肠搭桥手术逆转糖尿病表型并减少db/db小鼠肥胖
2型糖尿病(T2DM)是一种复杂的代谢紊乱,通常伴有体重增加,与进行性β细胞衰竭和胰岛素抵抗有关。减肥手术改善了葡萄糖耐量,提供了近乎完美的治疗。十二指肠-空肠旁路(DJB)是一种实验性手术,已在几种大鼠模型中进行了研究,但其对T2DM转基因模型db/db小鼠的影响尚不清楚。为了研究DJB对db/db小鼠的有效性,我们进行了手术并评估了代谢改善。结果显示,术后2周,DJB组小鼠体重明显低于sham组。与术前相比,术后空腹血糖(FBG)显著降低。统计分析显示,体重变化与空腹血糖有显著相关性。此外,DJB手术改变了血浆胰岛素水平,降低了约40%。因此,我们首次证明了DJB可以在重度T2DM和肥胖的转基因db/db小鼠中获得快速的治疗效果。此外,胰岛素水平下降反映DJB诱导的胰岛素敏感性提高。总之,我们的研究表明DJB手术可能是治疗肥胖相关T2DM的潜在有效方法。
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