Constantin Alina, Dumitrescu Mădălina, Nemecz Miruna, Picu Ariana, Smeu Bogdan, Guja Cristian, Alexandru Nicoleta, Georgescu Adriana, Tanko Gabriela
Pathophysiology and Pharmacology Department, Institute of Cellular Biology and Pathology 'Nicolae Simionescu' of the Romanian Academy, 8, BP Hasdeu Street, PO Box 35-14, 050568, Bucharest, Romania.
Institute of Diabetes, Nutrition and Metabolic Diseases "Prof. Dr N. Paulescu", Bucharest, Romania.
Obes Surg. 2019 May;29(5):1485-1497. doi: 10.1007/s11695-019-03710-0.
Pancreatic beta cells are highly sensitive to oxidative and endoplasmic reticulum (ER) stress, commonly occurring in type 2 diabetes (T2D) and obesity.
We aimed at investigating cellular responses of human beta cells exposed to sera from obese T2D patients treated differently, namely by conventional therapy or laparoscopic sleeve gastrectomy (LSG).
Serum samples from obese T2D men randomized to conventional treatment or LSG were taken at baseline and 6 months later. After exposing 1.1B4 cells to study patients' sera, the following were assessed: cellular viability and proliferation (by MTT and xCELLigence assays), reactive oxygen species (ROS) production (with DCFH-DA), and expression of ER stress markers, oxidative- or autophagy-related proteins and insulin (by real-time PCR and Western blot).
At 6-month follow-up, patients undergoing LSG achieved an adequate glycemic control, whereas conventionally treated patients did not. As compared to 1.1B4 cells incubated with baseline sera (control), cells exposed to sera from LSG-treated participants exhibited (i) increased viability and proliferation (p < 0.05); (ii) diminished levels of ROS and p53 (p < 0.05); (iii) enhanced protein expression of autophagy-related SIRT1 and p62/SQSTM1 (p < 0.05); (iv) significantly decreased transcript levels of ER stress markers (p < 0.05); and (v) augmented insulin expression (p < 0.05). Conversely, the 6-month conventional therapy appeared not to impact on circulating redox status. Moreover, 1.1B4 cells exposed to sera from conventionally treated patients experienced mild ER stress.
Circulating factors in patients with improved diabetes after metabolic surgery exerted favorable effects on beta cell function and survival.
胰腺β细胞对氧化应激和内质网（ER）应激高度敏感，这在2型糖尿病（T2D）和肥胖症中普遍存在。
我们旨在研究暴露于不同治疗方式的肥胖T2D患者血清中的人β细胞的细胞反应，这些治疗方式包括传统疗法或腹腔镜袖状胃切除术（LSG）。
对随机接受传统治疗或LSG的肥胖T2D男性患者，在基线和6个月后采集血清样本。将1.1B4细胞暴露于研究患者的血清后，评估以下指标：细胞活力和增殖（通过MTT和xCELLigence检测）、活性氧（ROS）生成（使用DCFH-DA）以及ER应激标志物、氧化或自噬相关蛋白和胰岛素的表达（通过实时PCR和蛋白质印迹法）。
在6个月的随访中，接受LSG的患者实现了充分的血糖控制，而接受传统治疗的患者则未实现。与用基线血清（对照）孵育的1.1B4细胞相比，暴露于LSG治疗参与者血清中的细胞表现出：（i）活力和增殖增加（p<0.05）；（ii）ROS和p53水平降低（p<0.05）；（iii）自噬相关的SIRT1和p62/SQSTM1蛋白表达增强（p<0.05）；（iv）ER应激标志物的转录水平显著降低（p<0.05）；以及（v）胰岛素表达增加（p<0.05）。相反，6个月的传统治疗似乎未影响循环氧化还原状态。此外,暴露于传统治疗患者血清中的1.1B4细胞经历了轻度ER应激。
代谢手术后糖尿病得到改善的患者体内的循环因子对β细胞功能和存活产生了有利影响。
