Diabetes recurrence after metabolic surgeries correlates with re-impaired insulin sensitivity rather than beta-cell function.
Diabetes recurrence after metabolic surgeries correlates with re-impaired insulin sensitivity rather than beta-cell function.
复制标题
代谢手术后糖尿病复发与胰岛素敏感性重新受损相关，而不是与β细胞功能相关。
DOI：
10.3748/wjg.v23.i19.3468
复制
发表时间：
2017-05-21
影响因子：
4.3
通讯作者：
Liu SZ
中科院分区：
文献类型：
--
作者：
Liu T;Zhong MW;Liu Y;Sun D;Wei M;Huang X;Cheng YG;Wu QZ;Wu D;Zhang XQ;Wang KX;Hu SY;Liu SZ
探讨袖状胃切除术（SG）和空肠-空肠转流术（DJB）后糖尿病复发的相关因素。对高脂饮食（HFD）和链脲佐菌素（STZ）诱导的糖尿病大鼠进行SG和DJB。术后4 wk用HFD诱导糖尿病复发。体重、口服葡萄糖耐量试验、胰岛素抵抗的稳态模型评估（HOMA-IR）、胰岛素信号传导[IR、肝脏和骨骼肌中的胰岛素受体底物（IRS）1、IRS 2、磷脂酰肌醇3-激酶和AKT]、口服葡萄糖刺激的胰岛素分泌、β细胞形态比较普通低脂饮食（SG-LFD）、高脂饮食（SG-HFD）、低脂饮食（SG-LFD）、高脂饮食（SG-HFD）、高脂饮食（SG-HFD）、高脂饮食（SG-LFD）、高脂饮食（SG-HFD）、高脂饮食（SG-HFD）和低脂饮食（SG-LFD）组大鼠的体重、细胞凋亡和胰岛素分泌、胰高血糖素样肽（GLP）-1、PYY和ghrelin的变化。在目标术后时间，DJB大鼠与LFD（DJB-LFD）、DJB与HFD（DJB-HFD）和假手术与LFD（Sham）。与Sham组相比，SG和DJB导致葡萄糖耐量显著改善，HOMA-IR降低，肝脏和肌肉胰岛素信号转导上调，口服葡萄糖刺激的胰岛素分泌水平较高，β细胞群较大，胰岛素免疫荧光强度较高，转移酶介导的dUTP-生物素3'缺口末端标记（TUNEL）阳性β细胞较少，餐后GLP-1和PYY水平较高。糖耐量的改善在术后12周被逆转。与SG-LFD组和DJB-LFD组相比，SG-HFD组和DJB-HFD组显示出更高的HOMA-IR，下调肝脏和肌肉胰岛素信号，以及更多的TUNEL阳性β细胞。HFD组和LFD组的体重、葡萄糖刺激的胰岛素分泌、β细胞质量、胰岛素免疫荧光强度以及餐后GLP-1和PYY水平无显著差异。SG组空腹血清ghrelin水平降低，HFD-SG组与LFD-SG组无差异。HFD逆转SG和DJB后葡萄糖稳态的改善。糖尿病复发可能与胰岛素敏感性再受损相关，但与β细胞功能和体重的改变无关。
To investigate factors causing diabetes recurrence after sleeve gastrectomy (SG) and duodenal-jejunal bypass (DJB). SG and DJB were performed on rats with diabetes induced by high-fat diet (HFD) and streptozotocin (STZ). HFD was used to induce diabetes recurrence at 4 wk postoperatively. Body weight, oral glucose tolerance test, homeostatic model assessment of insulin resistance (HOMA-IR), insulin signaling [IR, insulin receptor substrate (IRS)1, IRS2, phosphatidylinositol 3-kinase and AKT in liver and skeletal muscle], oral glucose stimulated insulin secretion, beta-cell morphology (mass, apoptosis and insulin secretion), glucagon-like peptide (GLP)-1, PYY and ghrelin were compared among SG rats with common low-fat diet (SG-LFD), SG with HFD (SG-HFD), DJB rats with LFD (DJB-LFD), DJB with HFD (DJB-HFD) and sham-operation with LFD (Sham) at targeted postoperative times. SG and DJB resulted in significant improvement in glucose tolerance, lower HOMA-IR, up-regulated hepatic and muscular insulin signaling, higher levels of oral glucose-stimulated insulin secretion, bigger beta-cell mass, higher immunofluorescence intensity of insulin, fewer transferase-mediated dUTP-biotin 3’ nick end-labeling (TUNEL)-positive beta cells and higher postprandial GLP-1 and PYY levels than in the Sham group. The improvement in glucose tolerance was reversed at 12 wk postoperatively. Compared with the SG-LFD and DJB-LFD groups, the SG-HFD and DJB-HFD groups showed higher HOMA-IR, down-regulated hepatic and muscular insulin signaling, and more TUNEL-positive beta cells. No significant difference was detected between HFD and LFD groups for body weight, glucose-stimulated insulin secretion, beta-cell mass, immunofluorescence intensity of insulin, and postprandial GLP-1 and PYY levels. Fasting serum ghrelin decreased in SG groups, and there was no difference between HFD-SG and LFD-SG groups. HFD reverses the improvement in glucose homeostasis after SG and DJB. Diabetes recurrence may correlate with re-impaired insulin sensitivity, but not with alterations of beta-cell function and body weight.