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Obesity Surgery
Published in: Obesity Surgery 5/2019

01-05-2019 | Obesity | Original Contributions

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

Authors: Alina Constantin, Mădălina Dumitrescu, Miruna Nemecz, Ariana Picu, Bogdan Smeu, Cristian Guja, Nicoleta Alexandru, Adriana Georgescu, Gabriela Tanko

Published in: Obesity Surgery | Issue 5/2019

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Abstract

Background

Pancreatic beta cells are highly sensitive to oxidative and endoplasmic reticulum (ER) stress, commonly occurring in type 2 diabetes (T2D) and obesity.

Objective

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).

Methods

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).

Results

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.

Conclusion

Circulating factors in patients with improved diabetes after metabolic surgery exerted favorable effects on beta cell function and survival.
Literature
1.
UK Prospective Diabetes Study Group. UK Prospective Diabetes Study 16. Overview of 6 years’ therapy of type II diabetes: a progressive disease. Diabetes. 1995;44(11):1249–58.CrossRef
2.
Fonseca V, McDuffie R, Calles J, et al. Determinants of weight gain in the action to control cardiovascular risk in diabetes trial. Diabetes Care. 2013;36:2162–8.CrossRefPubMedPubMedCentral
3.
Cummings DE, Rubino F. Metabolic surgery for the treatment of type 2 diabetes in obese individuals. Diabetologia. 2018;61(2):257–64.CrossRefPubMed
4.
Schauer PR, Bhatt DL, Kirwan JP, et al. Bariatric surgery versus intensive medical therapy for diabetes - 5-year outcomes. N Engl J Med. 2017;376:641–51.CrossRefPubMedPubMedCentral
5.
Ferrannini E, Mingrone G. Impact of different bariatric surgical procedures on insulin action and beta-cell function in type 2 diabetes. Diabetes Care. 2009;32(3):514–20.CrossRefPubMedPubMedCentral
6.
Dutia R, Brakoniecki K, Bunker P, et al. Limited recovery of β-cell function after gastric bypass despite clinical diabetes remission. Diabetes. 2014;63:1214–23.CrossRefPubMedPubMedCentral
7.
Fonseca SG, Gromada J, Urano F. Endoplasmic reticulum stress and pancreatic β-cell death. Trends Endocrinol Metab. 2011;22(7):266–74.PubMedPubMedCentral
8.
Walter P, Ron D. The unfolded protein response: from stress pathway to homeostatic regulation. Science. 2011;334(6059):1081–6.CrossRefPubMed
9.
Oyadomari S, Mori M. Roles of CHOP/GADD153 in endoplasmic reticulum stress. Cell Death Differ. 2004;11(4):381–9.CrossRefPubMed
10.
White MG, Shaw JA, Taylor R. Type 2 diabetes: the pathologic basis of reversible β-cell dysfunction. Diabetes Care. 2016;39(11):2080–8.CrossRefPubMed
11.
Leonetti F, Capoccia D, Coccia F, et al. Obesity, type 2 diabetes mellitus, and other comorbidities: a prospective cohort study of laparoscopic sleeve gastrectomy vs medical treatment. Arch Surg. 2012;147(8):694–700.CrossRefPubMed
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.
13.
Matthews DR, Hosker JP, Rudenski AS, et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412–9.CrossRefPubMed
14.
Hayes HL, Peterson BS, Haldeman JM, et al. Delayed apoptosis allows islet β-cells to implement an autophagic mechanism to promote cell survival. PLoS One. 2017;12(2):e0172567.CrossRefPubMedPubMedCentral
15.
16.
Motta MC, Divecha N, Lemieux M, et al. Mammalian SIRT1 represses forkhead transcription factors. Cell. 2004;116:551–63.CrossRefPubMed
17.
Luu L, Dai FF, Prentice KJ, et al. The loss of Sirt1 in mouse pancreatic beta cells impairs insulin secretion by disrupting glucose sensing. Diabetologia. 2013;56(9):2010–20.CrossRefPubMed
18.
Li Y, Xu S, Giles A, et al. Hepatic overexpression of SIRT1 in mice attenuates endoplasmic reticulum stress and insulin resistance in the liver. FASEB J. 2011;25:1664–79.CrossRefPubMedPubMedCentral
19.
Guo H, Chen Y, Liao L, et al. Resveratrol protects HUVECs from oxidized-LDL induced oxidative damage by autophagy upregulation via the AMPK/SIRT1 pathway. Cardiovasc Drugs Ther. 2013;27:189–98.CrossRefPubMed
20.
Geetha T, Zheng C, Vishwaprakash N, et al. Sequestosome 1/p62, a scaffolding protein, is a newly identified partner of IRS-1 protein. J Biol Chem. 2012;287(35):29672–8.CrossRefPubMedPubMedCentral
21.
Park JS, Oh SY, Lee DH, et al. p62/SQSTM1 is required for the protection against endoplasmic reticulum stress-induced apoptotic cell death. Free Radic Res. 2016;50(12):1408–21.CrossRefPubMed
22.
Kennedy J, Katsuta H, Jung MH, et al. Protective unfolded protein response in human pancreatic beta cells transplanted into mice. PLoS One. 2010;5:e11211.CrossRefPubMedPubMedCentral
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.PubMedPubMedCentral
24.
Synofzik M, Haack TB, Kopajtich R, et al. Absence of BiP co-chaperone DNAJC3 causes diabetes mellitus and multisystemic neurodegeneration. Am J Hum Genet. 2014;95(6):689–97.CrossRefPubMedPubMedCentral
25.
Wilhelm M, Schlegl J, Hahne H, et al. Mass-spectrometry-based draft of the human proteome. Nature. 2014;509:582–7.CrossRefPubMed
26.
Vogel C, Marcotte EM. Insights into the regulation of protein abundance from proteomic and transcriptomic analyses. Nat Rev Genet. 2012;13(4):227–32.CrossRefPubMedPubMedCentral
27.
Schwanhäusser B, Busse D, Li N, et al. Global quantification of mammalian gene expression control. Nature. 2011;473(7347):337–42.CrossRefPubMed
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.
29.
30.
Han J, Back SH, Hur J, et al. ER-stress-induced transcriptional regulation increases protein synthesis leading to cell death. Nat Cell Biol. 2013;15:481–90.CrossRefPubMedPubMedCentral
31.
Huang CJ, Lin CY, Haataja L, et al. High expression rates of human islet amyloid polypeptide induce endoplasmic reticulum stress mediated beta-cell apoptosis, a characteristic of humans with type 2 but not type 1 diabetes. Diabetes. 2007;56(8):2016–27.CrossRefPubMed
32.
Teodoro T, Odisho T, Sidorova E, et al. Pancreatic β-cells depend on basal expression of active ATF6α-p50 for cell survival even under non-stress conditions. Am J Physiol Cell Physiol. 2012;302:C992–1003.CrossRefPubMed
Metadata
Title
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
Authors
Alina Constantin
Mădălina Dumitrescu
Miruna Nemecz
Ariana Picu
Bogdan Smeu
Cristian Guja
Nicoleta Alexandru
Adriana Georgescu
Gabriela Tanko
Publication date
01-05-2019
Publisher
Springer US
Published in
Obesity Surgery / Issue 5/2019
Print ISSN: 0960-8923
Electronic ISSN: 1708-0428
DOI
https://doi.org/10.1007/s11695-019-03710-0

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