Han Haifeng, Hu Chunxiao, Wang Lei, Zhang Guangyong, Liu Shaozhuang, Li Feng, Sun Dong, Hu Sanyuan
Department of General Surgery, Qilu Hospital of Shandong University, 107#, Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China.
Obes Surg. 2014 Dec;24(12):2152-60. doi: 10.1007/s11695-014-1308-9.
Duodenal-jejunal bypass (DJB) surgery can induce rapid and durable remission of type 2 diabetes mellitus (T2DM), but the intrinsic mechanisms remain to be elucidated. Recent studies indicated that improved hepatic insulin resistance and insulin signaling transduction might contribute to the diabetic control after DJB. Given the important role of liver adiposity in hepatic insulin resistance, this study was aimed at investigating the effects of DJB on glucose homeostasis and liver fat accumulation in a T2DM rat model induced by high-fat diet (HFD) and small dose of streptozotocin (STZ).
Forty adult male diabetic rats induced by HFD and small dose of STZ were randomly assigned to sham and DJB groups. Body weight, calorie intake, hormone levels, glucose, and lipid parameters were measured at indicated time points. Subsequently, hepatic triglycerides (TG) content and the protein levels of sterol regulatory element binding protein-1 (SREBP-1), carbohydrate response element binding protein (ChREBP), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) were evaluated at 2 and 8 weeks postoperatively.
Compared with sham group, DJB induced rapid and significant improvements in glucose homeostasis and insulin sensitivity independently of weight loss and calorie restriction. The DJB-operated rats exhibited lower liver TG content and decreased hepatic SREBP-1, ChREBP, ACC, and FAS at 8 weeks postoperatively.
DJB alleviated hepatic fat accumulation and downregulated the key transcriptional regulators and enzymes involved in hepatic de novo lipogenesis, which might contribute to improved hepatic insulin sensitivity and glucose homeostasis after DJB.
十二指肠空肠旁路术（DJB）可迅速且持久地缓解2型糖尿病（T2DM），但其内在机制仍有待阐明。近期研究表明，改善肝脏胰岛素抵抗和胰岛素信号转导可能有助于DJB术后的糖尿病控制。鉴于肝脏脂肪在肝脏胰岛素抵抗中的重要作用，本研究旨在探讨DJB对高脂饮食（HFD）和小剂量链脲佐菌素（STZ）诱导的T2DM大鼠模型中葡萄糖稳态和肝脏脂肪蓄积的影响。
将40只由HFD和小剂量STZ诱导的成年雄性糖尿病大鼠随机分为假手术组和DJB组。在指定时间点测量体重、热量摄入、激素水平、血糖和血脂参数。随后，在术后2周和8周评估肝脏甘油三酯（TG）含量以及固醇调节元件结合蛋白-1（SREBP-1）、碳水化合物反应元件结合蛋白（ChREBP）、脂肪酸合酶（FAS）和乙酰辅酶A羧化酶（ACC）的蛋白水平。
与假手术组相比，DJB独立于体重减轻和热量限制，迅速且显著地改善了葡萄糖稳态和胰岛素敏感性。接受DJB手术的大鼠在术后8周时肝脏TG含量较低，肝脏SREBP-1、ChREBP、ACC和FAS水平降低。
DJB减轻了肝脏脂肪蓄积，并下调了肝脏从头脂肪生成中涉及的关键转录调节因子和酶，这可能有助于DJB术后肝脏胰岛素敏感性和葡萄糖稳态的改善。
