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

十二指肠-空肠旁路手术逆转db/db小鼠的糖尿病表型并减少肥胖

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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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