Abnormal expression of TRIAP1 and its role in gestational diabetes mellitus‑related pancreatic β cells

Li,Linxia; Yang,Kaihan; Ye,Fang; Xu,Yi; Cao,Lili; Sheng,Jia

doi:10.3892/etm.2021.9618

Abnormal expression of TRIAP1 and its role in gestational diabetes mellitus‑related pancreatic β cells

Authors:
- Linxia Li
- Kaihan Yang
- Fang Ye
- Yi Xu
- Lili Cao
- Jia Sheng
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Affiliations: Department of Obstetrics and Gynecology, Chengdu University, Chengdu, Sichuan 610106, P.R. China, Department of Biochemistry, Chengdu University, Chengdu, Sichuan 610106, P.R. China, Department of Internal Medicine, Chengdu University, Chengdu, Sichuan 610106, P.R. China, Department of Microbiological Immunology, Chengdu University, Chengdu, Sichuan 610106, P.R. China, Department of Nursing, Obstetrics and Gynecology, Hospital of Fudan University, Shanghai 200011, P.R. China
Published online on: January 7, 2021 https://doi.org/10.3892/etm.2021.9618
Article Number: 187
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Gestational diabetes mellitus (GDM) is a disease that is typically characterized by insulin resistance and pancreatic β cell dysfunction. Currently, the role of TP53‑regulated inhibitor of apoptosis 1 (TRIAP1) in the process of GDM remains to be elucidated. Therefore, the present study investigated the effects of TRIAP1 on GDM‑related pancreatic β cells. Reverse transcription‑quantitative PCR and western blot assays were conducted to analyze the expression levels of TRIAP1 in the peripheral blood of patients with GDM and subjects with healthy pregnancies. Subsequently, TRIAP1 small interfering RNA (siRNA), control siRNA, TRIAP1 plasmid and control plasmid were transfected into INS‑1 cells to assess the effects of TRIAP1 on pancreatic β cells. ELISA was used to assess the total insulin content and insulin secretion of pancreatic β cells. MTT and flow cytometry assays were performed to determine the viability and apoptosis of pancreatic β cells. The results demonstrated that TRIAP1 expression was downregulated in peripheral blood samples from patients with GDM. Transfection with TRIAP1 siRNA significantly decreased the levels of total insulin content and reduced insulin secretion in pancreatic β cells. In addition, downregulation of TRIAP1 in pancreatic β cells significantly induced cell apoptosis and reduced cell viability. Accordingly, transfection of INS1 cells with TRIAP1 siRNA increased the levels of the apoptosis‑associated genes apoptotic protease‑activating factor 1, caspase‑3, caspase‑7 and caspase‑9. However, transfection of the cells with TRIAP1 plasmid resulted in the opposite effects. TRIAP1 increased the growth of pancreatic β cells and their ability to secrete insulin, thus playing a protective role in GDM. The findings verified the effects and the underlying mechanism of TRIAP1 in pancreatic β cells and may provide additional clinical applications for the therapy of GDM.

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1	Zhen XM, Li X and Chen C: Longer-term outcomes in offspring of GDM mothers treated with metformin versus insulin. Diabetes Res Clin Pract. 144:82–92. 2018.PubMed/NCBI View Article : Google Scholar
2	Shan Z, Xu C, Wang W and Li W: Enhanced PDGF signaling in gestational diabetes mellitus is involved in pancreatic β-cell dysfunction. Biochem Biophys Res Commun. 516:402–407. 2019.PubMed/NCBI View Article : Google Scholar
3	Goueslard K, Cottenet J, Mariet AS, Giroud M, Cottin Y, Petit JM and Quantin C: Early cardiovascular events in women with a history of gestational diabetes mellitus. Cardiovasc Diabetol. 15(15)2016.PubMed/NCBI View Article : Google Scholar
4	Gunderson EP, Hurston SR, Dewey KG, Faith MS, Charvat-Aguilar N, Khoury VC, Nguyen VT and Quesenberry CP Jr: The study of women, infant feeding and type 2 diabetes after GDM pregnancy and growth of their offspring (SWIFT Offspring study): prospective design, methodology and baseline characteristics. BMC Pregnancy Childbirth. 15(150)2015.PubMed/NCBI View Article : Google Scholar
5	Wolpin BM, Bao Y, Qian ZR, Wu C, Kraft P, Ogino S, Stampfer MJ, Sato K, Ma J, Buring JE, et al: Hyperglycemia, insulin resistance, impaired pancreatic β-cell function, and risk of pancreatic cancer. J Natl Cancer Inst. 105:1027–1035. 2013.PubMed/NCBI View Article : Google Scholar
6	Malek R and Davis SN: Pharmacokinetics, efficacy and safety of glyburide for treatment of gestational diabetes mellitus. Expert Opin Drug Metab Toxicol. 12:691–699. 2016.PubMed/NCBI View Article : Google Scholar
7	Aberg AEB, Jönsson EK, Eskilsson I, Landin-Olsson M and Frid AH: Predictive factors of developing diabetes mellitus in women with gestational diabetes. Acta Obstet Gynecol Scand. 81:11–16. 2002.PubMed/NCBI View Article : Google Scholar
8	Alfadhli EM: Gestational diabetes mellitus. Saudi Med J. 36:399–406. 2015.PubMed/NCBI View Article : Google Scholar
9	Plows JF, Stanley JL, Baker PN, Reynolds CM and Vickers MH: The Pathophysiology of Gestational Diabetes Mellitus. Int J Mol Sci. 19(3342)2018.PubMed/NCBI View Article : Google Scholar
10	Li L, Wang S, Li H, Wan J, Zhou Q, Zhou Y and Zhang C: microRNA-96 protects pancreatic β-cell function by targeting PAK1 in gestational diabetes mellitus. Biofactors. 44:539–547. 2018.PubMed/NCBI View Article : Google Scholar
11	Chen C, Luo Y, Su Y and Teng L: The vitamin D receptor (VDR) protects pancreatic beta cells against Forkhead box class O1 (FOXO1)-induced mitochondrial dysfunction and cell apoptosis. Biomed Pharmacother. 117(109170)2019.PubMed/NCBI View Article : Google Scholar
12	Mandelbaum AD, Kredo-Russo S, Aronowitz D, Myers N, Yanowski E, Klochendler A, Swisa A, Dor Y and Hornstein E: miR-17-92 and miR-106b-25 clusters regulate beta cell mitotic checkpoint and insulin secretion in mice. Diabetologia. 62:1653–1666. 2019.PubMed/NCBI View Article : Google Scholar
13	Vejrazkova D, Vcelak J, Vankova M, Lukasova P, Bradnova O, Halkova T, Kancheva R and Bendlova B: Steroids and insulin resistance in pregnancy. J Steroid Biochem Mol Biol. 139:122–129. 2014.PubMed/NCBI View Article : Google Scholar
14	Hill DJ: Placental control of metabolic adaptations in the mother for an optimal pregnancy outcome What goes wrong in gestational diabetes? Placenta. 69:162–168. 2018.PubMed/NCBI View Article : Google Scholar
15	Brelje TC, Bhagroo NV, Stout LE and Sorenson RL: Beneficial effects of lipids and prolactin on insulin secretion and beta-cell proliferation: A role for lipids in the adaptation of islets to pregnancy. J Endocrinol. 197:265–276. 2008.PubMed/NCBI View Article : Google Scholar
16	Boehmer BH, Brown LD, Wesolowski SR, Hay WW Jr and Rozance PJ: Pulsatile hyperglycemia increases insulin secretion but not pancreatic β-cell mass in intrauterine growth-restricted fetal sheep. J Dev Orig Health Dis. 9:492–499. 2018.PubMed/NCBI View Article : Google Scholar
17	Weng Q, Zhao M, Zheng J, Yang L, Xu Z, Zhang Z, Wang J, Wang J, Yang B, Richard Lu Q, et al: STAT3 dictates β-cell apoptosis by modulating PTEN in streptozocin-induced hyperglycemia. Cell Death Differ. 27:130–145. 2020.PubMed/NCBI View Article : Google Scholar
18	Li T, Ni L, Zhao Z, Liu X, Lai Z, Di X, Xie Z, Song X, Wang X, Zhang R, et al: Melatonin attenuates smoking-induced hyperglycemia via preserving insulin secretion and hepatic glycogen synthesis in rats. J Pineal Res. 64(e12475)2018.PubMed/NCBI View Article : Google Scholar
19	Adams C, Cazzanelli G, Rasul S, Hitchinson B, Hu Y, Coombes RC, Raguz S and Yagüe E: Apoptosis inhibitor TRIAP1 is a novel effector of drug resistance. Oncol Rep. 34:415–422. 2015.PubMed/NCBI View Article : Google Scholar
20	Ketteler J, Panic A, Reis H, Wittka A, Maier P, Herskind C, Yagüe E, Jendrossek V and Klein D: Progression-related loss of stromal caveolin 1 levels mediates radiation resistance in prostate carcinoma via the apoptosis inhibitor TRIAP1. J Clin Med. 8(8)2019.PubMed/NCBI View Article : Google Scholar
21	Li Y, Tang X, He Q, Yang X, Ren X, Wen X, Zhang J, Wang Y, Liu N and Ma J: Overexpression of mitochondria mediator gene TRIAP1 by miR-320b loss is associated with progression in nasopharyngeal carcinoma. PLoS Genet. 12(e1006183)2016.PubMed/NCBI View Article : Google Scholar
22	Miliara X, Garnett JA, Tatsuta T, Abid Ali F, Baldie H, Pérez-Dorado I, Simpson P, Yague E, Langer T and Matthews S: Structural insight into the TRIAP1/PRELI-like domain family of mitochondrial phospholipid transfer complexes. EMBO Rep. 16:824–835. 2015.PubMed/NCBI View Article : Google Scholar
23	Alyes VLF, Zanatta DB, de Oliveira MB, Eugenio AIP, Fernando RC, Strauss BE and Colleoni GWB: Silencing of apoptosome regulating genes, HSP70 and TRIAP1, induces apoptosis in MM cell lines In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research, Philadelphia, PA, 2015. Cancer Res. 75 (Suppl 15)(Abstract nr 1017)2015.
24	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar
25	Zhong B, Ma S and Wang DH: TRPV1 mediates glucose-induced insulin secretion through releasing neuropeptides. In Vivo. 33:1431–1437. 2019.PubMed/NCBI View Article : Google Scholar
26	Seshiah V, Kalra S, Gupte S, Divakar H, Murugananthan A, Banerjee S, Gupta S, Balaji V, Zargar A, Das A, et al: Classification of hyperglycemia in pregnancy. Indian J Endocrinol Metab. 18:445–448. 2014.PubMed/NCBI View Article : Google Scholar
27	Dessì A, Marincola FC and Fanos V: Metabolomics and the great obstetrical syndromes - GDM, PET, and IUGR. Best Pract Res Clin Obstet Gynaecol. 29:156–164. 2015.PubMed/NCBI View Article : Google Scholar
28	Naseh A, Ashrafzadeh S and Rassi S: Prevalence of vitamin D deficiency in pregnant mothers in Tehran and investigating its association with serum glucose and insulin. J Matern Fetal Neonatal Med. 31:2312–2318. 2018.PubMed/NCBI View Article : Google Scholar
29	Wang C, Zhu WW, Wei YM, Feng H, Su R and Yang HX: Exercise intervention during pregnancy can be used to manage weight gain and improve pregnancy outcomes in women with gestational diabetes mellitus. BMC Pregnancy Childbirth. 15(255)2015.PubMed/NCBI View Article : Google Scholar
30	Xu K, Bian D, Hao L, Huang F, Xu M, Qin J and Liu Y: microRNA-503 contribute to pancreatic beta cell dysfunction by targeting the mTOR pathway in gestational diabetes mellitus. EXCLI J. 16:1177–1187. 2017.PubMed/NCBI View Article : Google Scholar
31	Zhang YL and Chen XQ: Dysregulation of microRNA-770-5p influences pancreatic-β-cell function by targeting TP53 regulated inhibitor of apoptosis 1 in gestational diabetes mellitus. Eur Rev Med Pharmacol Sci. 24:793–801. 2020.PubMed/NCBI View Article : Google Scholar
32	Boland BB, Rhodes CJ and Grimsby JS: The dynamic plasticity of insulin production in β-cells. Mol Metab. 6:958–973. 2017.PubMed/NCBI View Article : Google Scholar
33	Jian X and Felsenfeld G: Insulin promoter in human pancreatic β cells contacts diabetes susceptibility loci and regulates genes affecting insulin metabolism. Proc Natl Acad Sci USA. 115:E4633–E4641. 2018.PubMed/NCBI View Article : Google Scholar
34	Miyakoshi K, Tanaka M, Saisho Y, Shimada A, Minegishi K, Kim SH, Asai S, Itoh H and Yoshimura Y: Pancreatic beta-cell function and fetal growth in gestational impaired glucose tolerance. Acta Obstet Gynecol Scand. 89:769–775. 2010.PubMed/NCBI View Article : Google Scholar
35	Fook-Alves VL, de Oliveira MB, Zanatta DB, Strauss BE and Colleoni GWB: TP53 regulated inhibitor of apoptosis 1 (TRIAP1) stable silencing increases late apoptosis by upregulation of caspase 9 and APAF1 in RPMI8226 multiple myeloma cell line. Biochim Biophys Acta. 1862:1105–1110. 2016.PubMed/NCBI View Article : Google Scholar
36	Potting C, Tatsuta T, König T, Haag M, Wai T, Aaltonen MJ and Langer T: TRIAP1/PRELI complexes prevent apoptosis by mediating intramitochondrial transport of phosphatidic acid. Cell Metab. 18:287–295. 2013.PubMed/NCBI View Article : Google Scholar
37	Lorenzo-Almorós A, Hang T, Peiró C, Soriano-Guillén L, Egido J, Tuñón J and Lorenzo Ó: Predictive and diagnostic biomarkers for gestational diabetes and its associated metabolic and cardiovascular diseases. Cardiovasc Diabetol. 18(140)2019.PubMed/NCBI View Article : Google Scholar
38	Wójcik M, Mac-Marcjanek K, Woźniak LA, Nadel I, Lewiński A and Cypryk K: The association of leukocyte phosphatidylinositol 3-kinase delta overexpression with gestational diabetes mellitus (GDM). Endokrynol Pol. 65:17–24. 2014.PubMed/NCBI View Article : Google Scholar