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

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

doi:10.2174/2213988501711010041

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.

Highlights

Type 2 Diabetes Mellitus (T2DM) and obesity, two types of metabolic homeostasis disorders, have become global epidemics
The present study investigated how Duodenal-Jejunal Bypass (DJB) procedure affected metabolic homeostasis and obesity in db/db mice, a leptin receptor deficiency T2DM animal model
We confirmed that as a metabolic modification procedure by bypassing duodenum and proximal jejunum, DJB surgery is beneficial toward resolving hyperglycemia and lowering body weight in this profound obese and T2DM animal model

Summary

Introduction

Type 2 Diabetes Mellitus (T2DM) and obesity, two types of metabolic homeostasis disorders, have become global epidemics. As a glucose homeostasis impaired disease, interactions between obesity and inadequate pancreatic β-cell response to the progressive insulin resistance result in T2DM. Obesity, another epidemic induced by disturbed energy-balance regulation, has influenced about 2 billion people worldwide [2]. Obese patients having prediabetes are characterized with insulin resistance and at the same time 17% of these people will develop T2DM within 4 years. Better lifestyle establishment and pharmaceutical interventions should be firstline and second-line treatment respectively for curing T2DM and obesity, success is difficult to achieve. An emerging treatment, provides long-term remission of T2DM and sustained weight loss [3 - 5]

Methods

Results

Conclusion