Laboratório de Fisiologia Endócrina e Metabolismo, Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná (UNIOESTE), Cascavel, PR, Brazil.
Universidade Federal do Rio de Janeiro, Campus UFRJ-Macaé, Macaé, RJ, Brazil.
Endocrine. 2018 Jun;60(3):407-414. doi: 10.1007/s12020-018-1578-4. Epub 2018 Mar 19.
Duodeno-jejunal bypass (DJB) operation improves glucose homeostasis in morbid obesity, independently of weight loss or reductions in adiposity, through mechanisms not yet fully elucidated. Herein, we evaluated the effects of DJB upon glucose homeostasis, endocrine pancreatic morphology, and β-cell responsiveness to potentiating agents of cholinergic and cAMP pathways, in western diet (WD) obese rats, at 2 months after operation.
From 8 to 18 weeks of age male Wistar rats fed on a WD. After this period, a sham (WD Sham group) or DJB (WD DJB) operations were performed. At 2 months after operation glucose homeostasis was verified.
Body weight was similar between WD DJB and WD Sham rats, but WD DJB rats showed a decrease in Lee index, retroperitoneal and perigonadal fat pads. Also, WD DJB rats displayed reduced fasting glycemia and insulinemia, and increased insulin-induced Akt activation in the gastrocnemius. Islets from WD DJB rats secreted less amounts of insulin, in response to activators of the cholinergic (carbachol and phorbol 12-myristate 13-acetate) and cAMP (forskolin and 3-isobutyl-1-methyl-xantine) pathways. Islets of WD DJB rats had higher sintaxin-1 protein content than WD Sham, but without modification in muscarinic-3 receptor, protein kinase (PK)-Cα, and (PK)-Aα protein amounts. In addition, islets of WD DJB animals showed reduction in islets and β-cell masses.
DJB surgery improves fasting glycemia and insulin action in skeletal muscle. Better endocrine pancreatic morphofunction was associated, at least in part, with the regulation of the cholinergic and cAMP pathways, and improvements in syntaxin-1 islet protein content induced by DJB.
通过尚未完全阐明的机制，十二指肠空肠旁路（DJB）手术可改善病态肥胖患者的葡萄糖稳态，独立于体重减轻或脂肪减少。在此，我们评估了 DJB 对葡萄糖稳态、内分泌胰腺形态以及β细胞对胆碱能和 cAMP 通路增强剂的反应性的影响，在手术后 2 个月的西方饮食（WD）肥胖大鼠中。
雄性 Wistar 大鼠从 8 至 18 周龄开始喂食 WD。在此期间，进行假手术（WD Sham 组）或 DJB（WD DJB）手术。手术后 2 个月，验证葡萄糖稳态。
WD DJB 和 WD Sham 大鼠的体重相似，但 WD DJB 大鼠的 Lee 指数、腹膜后和性腺周围脂肪垫减少。此外，WD DJB 大鼠空腹血糖和胰岛素血症降低，腓肠肌中胰岛素诱导的 Akt 激活增加。WD DJB 大鼠胰岛对胆碱能（卡巴胆碱和佛波醇 12-肉豆蔻酸 13-乙酸酯）和 cAMP（forskolin 和 3-异丁基-1-甲基黄嘌呤）通路的激活剂的胰岛素分泌减少。WD DJB 大鼠胰岛的 syntaxin-1 蛋白含量高于 WD Sham，但没有改变毒蕈碱-3 受体、蛋白激酶（PK）-Cα 和（PK）-Aα 蛋白含量。此外，WD DJB 动物的胰岛和β细胞质量减少。
DJB 手术可改善空腹血糖和骨骼肌胰岛素作用。更好的内分泌胰腺形态功能与胆碱能和 cAMP 通路的调节以及 DJB 诱导的 syntaxin-1 胰岛蛋白含量的改善有关。
