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
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.
KeywordsHuman 1.1B4 beta cells Obesity Type 2 diabetes Oxidative stress ER stress Laparoscopic sleeve gastrectomy
We are grateful to all the patients who participated in this study. We would like to thank Dr. Daniela Lixandru (Carol Davila University of Medicine and Pharmacy, Bucharest) for providing the 1.1B4 pancreatic beta cells. We also acknowledge the valuable technical assistance of Ms. Marilena Isachi and Ms. Marcela Toader.
This study was supported by the Romanian National Authority for Scientific Research and Innovation, CNCS-UEFISCDI, through the projects PN-II-PT-PCCA-2013-4-2154, PN-III-P1-1.2-PCCDI-2017-0797, and PN-III-P1-1.2-PCCDI-2017-0527 and by the Romanian Academy.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
Informed consent was obtained from all individual participants included in the study.
Statement of Human and Animal Rights
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and /or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
- 7.Fonseca SG, Gromada J, Urano F. Endoplasmic reticulum stress and pancreatic β-cell death. Trends Endocrinol Metab. 2011;22(7):266–74.Google Scholar
- 12.Stefan DS, Mihai A, Bajko D, et al. Comparison of sleeve gastrectomy and conservatory treatment effect on biochemical and hormonal profile of obese type 2 diabetes subjects: CREDOR randomized controlled study results. Rev.Chim. 2017;68(7):1622–7.Google Scholar
- 23.Yang H, Liu R, Cui Z, et al. Functional characterization of 58-kilodalton inhibitor of protein kinase in protecting against diabetic retinopathy via the endoplasmic reticulum stress pathway. Mol Vis. 2011;17:78–84.Google Scholar
- 28.Liew H-K, Chen P-K, Peng H-F, et al. Downregulation of GRP78 chaperone protein triggers pro-apoptotic CHOP signaling cascade in acute intracerebral hemorrhage rats. FASEB J. 2017;31(1 Suppl):815.5.Google Scholar