Combination of Sleeve Gastrectomy and Mesenchymal Stem Cells Improves Insulin Resistance by Modulating Pro-inflammatory Milieu in Obese Type 2 Diabetic Rat Model

Vito Mahendra Ekasaputra; Abdul Mughni; Agung Putra; Ignatius Riwanto; Dimas Erlangga Nugrahadi; Anggoro Prasetya; Indra Putranto; Iffan Alif; Fadli Rizal Makarim

doi:10.3889/oamjms.2022.8211

Authors

Vito Mahendra Ekasaputra Department of Surgery, Faculty of Medicine, Diponegoro University, Kariadi Hospital, Semarang, Indonesia; Department of Surgery, Faculty of Medicine, Sultan Agung Islamic University, Semarang, Indonesia
Abdul Mughni Department of Digestive Surgery, Faculty of Medicine, Diponegoro University, Kariadi Hospital, Semarang, Indonesia https://orcid.org/0000-0001-7631-2906
Agung Putra Stem Cell and Cancer Research, Faculty of Medicine, Sultan Agung Islamic University, Semarang, Indonesia; Department of Pathological Anatomy, Faculty of Medicine, Sultan Agung Islamic University, Semarang, Indonesia; Department of Postgraduate Biomedical Science, Faculty of Medicine, Sultan Agung Islamic University, Semarang, Indonesia https://orcid.org/0000-0003-4261-9437
Ignatius Riwanto Department of Digestive Surgery, Faculty of Medicine, Diponegoro University, Kariadi Hospital, Semarang, Indonesia
Dimas Erlangga Nugrahadi Department of Digestive Surgery, Faculty of Medicine, Diponegoro University, Kariadi Hospital, Semarang, Indonesia
Anggoro Prasetya Department of Surgery, Faculty of Medicine, Diponegoro University, Kariadi Hospital, Semarang, Indonesia
Indra Putranto Department of Surgery, Faculty of Medicine, Diponegoro University, Kariadi Hospital, Semarang, Indonesia
Iffan Alif Stem Cell and Cancer Research, Faculty of Medicine, Sultan Agung Islamic University, Semarang, Indonesia https://orcid.org/0000-0003-1231-9185
Fadli Rizal Makarim Department of Pathological Anatomy, Faculty of Medicine, Sultan Agung Islamic University, Semarang, Indonesia

DOI:

https://doi.org/10.3889/oamjms.2022.8211

Keywords:

Obesity, Diabetes mellitus, Sleeve gastrectomy, Mesenchymal stem cells, Insulin resistance

Abstract

ABSTRACT

Background: Obesity is a major risk factor for the onset of insulin resistance and type 2 diabetes mellitus (T2DM) caused by chronic inflammation of the islets of langerhans. Sleeve gastrectomy (SG) procedure increases particular hormone which stimulates insulin sensitivity. Mesenchymal stem cells (MSCs) can also exhibit potential immunomodulatory properties through their paracrine effects, however the mechanism regarding combination of them could not be adequately explained.

Aim: In this study, we explore the potential of sleeve gastrectomy followed by injection of MSCs in type 2 diabetic rats with obesity in improving insulin resistance.

Methods: This study used a pre and post control group design with 18 rats that divided into 3 groups: control (C), sleeve gastrectomy (SG), sleeve gastrectomy + MSCs (SG+M). On day 10, the level of IL-6, IL-10 and HOMA-IR were evaluated using ELISA.

Results: This study showed a significant decrease of IL-6 level in all treatment groups on day 10, in which SG+M group showed optimum inhibition. This result was in line with the optimum increase of IL-10 in SG+M group. Moreover, our study also revealed the optimum decrease of HOMA-IR in SG+M group on day 10.

Conclusion: Combination of SG and MSCs can optimally improve insulin resistance by modulating proinflammatory milieu though inhibiting IL-6 level and upregulating IL-10 level in obese type 2 diabetes mellitus rat model.

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References

Morton JM. The ASMBS Textbook of Bariatric Surgery. 2nd ed. Springer; 2020.

McArdle MA, Finucane OM, Connaughton RM, McMorrow AM, Roche HM. Mechanisms of obesity-induced inflammation and insulin resistance: Insights into the emerging role of nutritional strategies. Front Endocrinol (Lausanne). 2013;4:1-23. https://doi.org/10.3389/fendo.2013.00052 PMid:23675368 DOI: https://doi.org/10.3389/fendo.2013.00052

Nicolas W. Cortes-Penfield, Barbara W. Trautner RJ. Orexin activation counteracts decreases in nonexercise activity thermogenesis (NEAT) caused by high-fat diet. Physiol Behav. 2017;176(5):139-48. https://doi.org/10.1016/j.physbeh.2017.03.040 PMid:28363838 DOI: https://doi.org/10.1016/j.physbeh.2017.03.040

Biobaku F, Ghanim H, Monte SV, Caruana JA, Dandona P. Bariatric surgery: Remission of inflammation, cardiometabolic benefits, and common adverse effects. J Endocr Soc. 2020;4(9):bvaa049. PMid:32775937 DOI: https://doi.org/10.1210/jendso/bvaa049

Kassem MA, Durda MA, Stoicea N, Cavus O, Sahin L, Rogers B. The impact of bariatric surgery on Type 2 diabetes mellitus and the management of hypoglycemic events. Front Endocrinol (Lausanne). 2017;8:37. https://doi.org/10.3389/fendo.2017.00037 PMid:28298900 DOI: https://doi.org/10.3389/fendo.2017.00037

Putra A, Rosdiana I, Darlan DM, Alif I, Hayuningtyas F, Wijaya I, et al. Intravenous administration is the best route of mesenchymal stem cells migration in improving liver function enzyme of acute liver failure. Folia Med (Plovdiv). 2020;62(1):52-8. https://doi.org/10.3897/folmed.e47712 PMid:32337897 DOI: https://doi.org/10.3897/folmed..e47712

Putra A, Sa’diyah NA, Rahmalita A, et al. The effect of mesenchymal stem cells on the endothelial cells of diabetic mice. In: Hofstra R, Koibuchi N, Fucharoen S, editors. Proceeding of 4th BIBMC and 2nd ACMM. Vol. 4. Boca Raton, Florida: CRC Press; 2017. p. 57-60. DOI: https://doi.org/10.1201/9781315208619-13

Pawitan JA, Yang Z, Wu YN, Lee EH. Towards standardized stem cell therapy in Type 2 diabetes mellitus: A systematic review. Curr Stem Cell Res Ther. 2018;13(6):476-88. PMid:29732994 DOI: https://doi.org/10.2174/1574888X13666180502143657

Burhans MS, Hagman DK, Kuzma JN, Schmidt KA, Kratz M. Contribution of adipose tissue inflammation to the development of Type 2 diabetes mellitus. Compr Physiol. 2018;9(1):1-58. https://doi.org/10.1002/cphy.c170040 PMid:30549014 DOI: https://doi.org/10.1002/cphy.c170040

Muhar AM, Putra A, Warli SM, Munir D. Hypoxia-mesenchymal stem cells inhibit intra-peritoneal adhesions formation by upregulation of the il-10 expression. Open Access Maced J Med Sci. 2019;7(23):3937-43. https://doi.org/10.3889/oamjms.2019.713 PMid:32165932 DOI: https://doi.org/10.3889/oamjms.2019.713

Muhar AM, Putra A, Ekasaputra VM, Darlan DM, Paramita DA, Adeputra Nasution IP. Mesenchymal stem cells under hypoxia condition inhibit peritoneal adhesion by suppressing the prolonged release of interleukin-6. Med Glas (Zenica). 2021;18(2):398-403. https://doi.org/10.17392/1304-21 PMid:34212709

Wang M, Song L, Strange C, Dong X, Wang H. Therapeutic effects of adipose stem cells from diabetic mice for the treatment of Type 2 diabetes. Mol Ther. 2018;26(8):1921-30. https://doi.org/10.1016/j.ymthe.2018.06.013 PMid:30005867 DOI: https://doi.org/10.1016/j.ymthe.2018.06.013

Abdalla MM. Ghrelin physiological functions and regulation. Eur Endocrinol. 2015;11(2):90-5. https://doi.org/10.17925/EE.2015.11.02.90 PMid:29632576 DOI: https://doi.org/10.17925/EE.2015.11.02.90

Darlan DM, Munir D, Jusuf NK, Putra A, Ikhsan R, Alif I. In vitro regulation of IL-6 and TGF-ß by mesenchymal stem cells in systemic lupus erythematosus patients. Med Glas (Zenica). 2020;17(2):408-13. https://doi.org/10.17392/1186-20 PMid:32602296

Niemand C, Nimmesgern A, Haan S, Fischer P, Schaper F, Rossaint R, et al. Activation of STAT3 by IL-6 and IL-10 in primary human macrophages is differentially modulated by suppressor of cytokine signaling 3. J Immunol. 2003;170(6):3263-72. https://doi.org/10.4049/jimmunol.170.6.3263 PMid:12626585 DOI: https://doi.org/10.4049/jimmunol.170.6.3263

Copps KD, White MF. Regulation of insulin sensitivity by serine/threonine phosphorylation of insulin receptor substrate proteins IRS1 and IRS2. Diabetologia. 2012;55(10):2565-82. https://doi.org/10.1007/s00125-012-2644-8 PMid:22869320 DOI: https://doi.org/10.1007/s00125-012-2644-8

Chen L, Chen R, Wang H, Liang F. mechanisms linking inflammation to insulin resistance. Int J Endocrinol. 2015;2015:508409. https://doi.org/10.1155/2015/508409 PMid:26136779 DOI: https://doi.org/10.1155/2015/508409

Kotikalapudi N, Sampath SJ, Narayan SS, Bhonde R, Nemani H, Mungamuri SK, et al. The promise(s) of mesenchymal stem cell therapy in averting preclinical diabetes: Lessons from in vivo and in vitro model systems. Sci Rep. 2021;11(1):16983. https://doi.org/10.1038/s41598-021-96121-0 PMid:34417511 DOI: https://doi.org/10.1038/s41598-021-96121-0