Sera of Obese Type 2 Diabetic Patients Undergoing Metabolic Surgery Instead of Conventional Treatment Exert Beneficial Effects on Beta Cell Survival and Function: Results of a Randomized Clinical Study.

Abstract

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 6months 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.