Candidate genes associated with the effect of rosiglitazone on glycemic control and cardiovascular system in the treatment of type 2 diabetes mellitus

Wu,Xiaoli

doi:10.3892/etm.2019.7160

Candidate genes associated with the effect of rosiglitazone on glycemic control and cardiovascular system in the treatment of type 2 diabetes mellitus

Authors:
- Xiaoli Wu
View Affiliations

Affiliations: Department of Pharmacy, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China
Published online on: January 9, 2019 https://doi.org/10.3892/etm.2019.7160
Pages: 2039-2046
Copyright: © Wu . This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

In the present study, candidate genes affected by rosiglitazone to exert glycemic control in the treatment of type 2 diabetes mellitus (T2DM) and associated with its adverse cardiovascular effects were identified using a bioinformatics analysis. The gene expression profiles of the dataset GSE36875 from the Gene Expression Omnibus database, including heart samples from 5 non‑diabetic control mice (NC), 5 untreated diabetic mice (NH) and 5 rosiglitazone‑treated diabetic mice (TH), were used to identify differentially expressed genes (DEGs) in the NC vs. NH, NC vs. TH and TH vs. NH groups. Subsequently, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enriched by the DEGs were determined. Furthermore, genes associated with the action of rosiglitazone were identified using Short Time‑series Expression Miner, which were then subjected to enrichment analysis in gene ontology (GO) terms in the category biological process (BP), and networks of the GO terms, KEGG pathways and genes associated with the action of rosiglitazone were constructed. Finally, biological abnormalities associated with these genes were identified using WebGestalt. A set of 791 DEGs in three groups (NC vs. NH, NC vs. TH and NH vs. TH) were identified. Subsequently, 72 DEGs [e.g., apolipoprotein (Apo)A1, ApoA5, cytochrome P450 (Cyp)2c37, Cyp2J5, Cyp2b9 and Cyp2b10] were identified as genes associated with the action of rosiglitazone. In addition, a network of 13 GO terms in the category BP, 6 KEGG pathways and 41 genes associated with the action of rosiglitazone was constructed, with major terms/pathways including oxidation/reduction, lipid transport, peroxisome proliferator‑activated receptor signaling pathway and metabolism of xenobiotics by Cyp. Finally, 15 biological abnormalities (including abnormal triglyceride levels, abnormal cholesterol homeostasis, abnormal lipid homeostasis) associated with these genes were identified. ApoA1, ApoA5, Cyp2c37, Cyp2J5, Cyp2b9 and Cyp2b10 were differently expressed after rosiglitazone treatment, which may be accountable for affecting cardiovascular outcomes and glycemic control in T2DM. The present results may expand the current understanding of the mechanism of action of rosiglitazone to exert glycemic control in T2DM, as well as its effects on the cardiovascular system.

View Figures

View References

1	Dall TM, Yang W, Halder P, Pang B, Massoudi M, Wintfeld N, Semilla AP, Franz J and Hogan PF: The economic burden of elevated blood glucose levels in 2012: Diagnosed and undiagnosed diabetes, gestational diabetes mellitus, and prediabetes. Diabetes Care. 37:3172–3179. 2014. View Article : Google Scholar : PubMed/NCBI
2	American Diabetes Association: Diagnosis and classification of diabetes mellitus. Diabetes Care. 37 Suppl 1:S81–S90. 2014. View Article : Google Scholar : PubMed/NCBI
3	Cooper ME, White MF, Zick Y and Zimmet P: Type 2 diabetes mellitus. https://www.nature.com/nrendo/posters/type2diabetesmellitus/index.htmlOctober. 2012
4	Cockram C: The epidemiology of diabetes mellitus in the Asia-Pacific region. Hong Kong Med J. 6:43–52. 2000.PubMed/NCBI
5	Bazargan M, Foster DJR, Davey AK and Muhlhausler BS: Rosiglitazone metabolism in human liver microsomes using a substrate depletion method. Drugs R D. 17:189–198. 2017. View Article : Google Scholar : PubMed/NCBI
6	Abou Daya K, Abu Daya H, Nasser Eddine M, Nahhas G and Nuwayri-Salti N: Effects of rosiglitazone (PPAR γ agonist) on the myocardium in non-hypertensive diabetic rats (PPAR γ). J Diabetes. 7:85–94. 2015. View Article : Google Scholar : PubMed/NCBI
7	Mayerson AB, Hundal RS, Dufour S, Lebon V, Befroy D, Cline GW, Enocksson S, Inzucchi SE, Shulman GI and Petersen KF: The effects of rosiglitazone on insulin sensitivity, lipolysis, and hepatic and skeletal muscle triglyceride content in patients with type 2 diabetes. Diabetes. 51:797–802. 2002. View Article : Google Scholar : PubMed/NCBI
8	Sundaresan A, Radhiga T and Pugalendi KV: Effect of ursolic acid and Rosiglitazone combination on hepatic lipid accumulation in high fat diet-fed C57BL/6J mice. Eur J Pharmacol. 741:297–303. 2014. View Article : Google Scholar : PubMed/NCBI
9	Bajpeyi S, Pasarica M, Conley KE, Newcomer BR, Jubrias SA, Gamboa C, Murray K, Sereda O, Sparks LM and Smith SR: Pioglitazone-induced improvements in insulin sensitivity occur without concomitant changes in muscle mitochondrial function. Metabolism. 69:24–32. 2017. View Article : Google Scholar : PubMed/NCBI
10	Pedram A, Razandi M, Blumberg B and Levin ER: Membrane and nuclear estrogen receptor α collaborate to suppress adipogenesis but not triglyceride content. FASEB J. 30:230–240. 2016. View Article : Google Scholar : PubMed/NCBI
11	Nissen SE and Wolski K: Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 356:2457–2471. 2007. View Article : Google Scholar : PubMed/NCBI
12	Singh S, Loke YK and Furberg CD: Long-term risk of cardiovascular events with rosiglitazone: A meta-analysis. JAMA. 298:1189–1195. 2007. View Article : Google Scholar : PubMed/NCBI
13	Home PD, Pocock SJ, Beck-Nielsen H, Curtis PS, Gomis R, Hanefeld M, Jones NP, Komajda M and McMurray JJ; RECORD Study Team, : Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): A multicentre, randomised, open-label trial. Lancet. 373:2125–2135. 2009. View Article : Google Scholar : PubMed/NCBI
14	Wilson KD, Li Z, Wagner R, Yue P, Tsao P, Nestorova G, Huang M, Hirschberg DL, Yock PG, Quertermous T and Wu JC: Transcriptome alteration in the diabetic heart by rosiglitazone: Implications for cardiovascular mortality. PLoS One. 3:e26092008. View Article : Google Scholar : PubMed/NCBI
15	Rao Y, Lee Y, Jarjoura D, Ruppert AS, Liu CG, Hsu JC and Hagan JP: A comparison of normalization techniques for microRNA microarray data. Stat Appl Genet Mol Biol. 7:Article22. 2008. View Article : Google Scholar : PubMed/NCBI
16	Gentleman R, Carey V, Huber W, Irizarry R and Dudoit S: Bioinformatics and computational biology solutions using R and Bioconductor. Springer Science & Business Media. 2006.
17	Szekely GJ and Rizzo ML: Hierarchical clustering via joint between-within distances: Extending Ward's minimum variance method. J Classification. 22:151–183. 2005. View Article : Google Scholar
18	Ernst J and Bar-Joseph Z: STEM: A tool for the analysis of short time series gene expression data. BMC Bioinformatics. 7:1912006. View Article : Google Scholar : PubMed/NCBI
19	Wang Z, Shang P, Li Q, Wang L, Chamba Y, Zhang B, Zhang H and Wu C: iTRAQ-based proteomic analysis reveals key proteins affecting muscle growth and lipid deposition in pigs. Sci Rep. 7:467172017. View Article : Google Scholar : PubMed/NCBI
20	Duong PT, Collins HL, Nickel M, Lund-Katz S, Rothblat GH and Phillips MC: Characterization of nascent HDL particles and microparticles formed by ABCA1-mediated efflux of cellular lipids to apoA-I. J Lipid Res. 47:832–843. 2006. View Article : Google Scholar : PubMed/NCBI
21	Llaverias G, Rebollo A, Pou J, Vázquez-Carrera M, Sánchez RM, Laguna JC and Alegret M: Effects of rosiglitazone and atorvastatin on the expression of genes that control cholesterol homeostasis in differentiating monocytes. Biochem Pharmacol. 71:605–614. 2006. View Article : Google Scholar : PubMed/NCBI
22	Li C, Tu Y, Liu TR, Guo ZG, Xie D, Zhong JK, Fan YZ and Lai WY: Rosiglitazone attenuates atherosclerosis and increases high-density lipoprotein function in atherosclerotic rabbits. Int J Mol Med. 35:715–723. 2015. View Article : Google Scholar : PubMed/NCBI
23	Jin X, Sviridov D, Liu Y, Vaisman B, Addadi L, Remaley AT and Kruth HS: ABCA1 (ATP-binding cassette transporter A1) mediates ApoA-I (Apolipoprotein A-I) and ApoA-I mimetic peptide mobilization of extracellular cholesterol microdomains deposited by macrophages. Arterioscler Thromb Vasc Biol. 36:2283–2291. 2016. View Article : Google Scholar : PubMed/NCBI
24	Liu X, Ren K, Suo R, Xiong SL, Zhang QH, Mo ZC, Tang ZL, Jiang Y, Peng XS and Yi GH: ApoA-I induces S1P release from endothelial cells through ABCA1 and SR-BI in a positive feedback manner. J Physiol Biochem. 72:657–667. 2016. View Article : Google Scholar : PubMed/NCBI
25	Li D, Weng S, Yang B, Zander DS, Saldeen T, Nichols WW, Khan S and Mehta JL: Inhibition of arterial thrombus formation by ApoA1 Milano. Arterioscler Thromb Vasc Biol. 19:378–383. 1999. View Article : Google Scholar : PubMed/NCBI
26	Wang Y, Lu Z, Zhang J, Yang Y, Shen J, Zhang X and Song Y: The APOA5 rs662799 polymorphism is associated with dyslipidemia and the severity of coronary heart disease in Chinese women. Lipids Health Dis. 15:1702016. View Article : Google Scholar : PubMed/NCBI
27	Oliva I, Guardiola M, Vallvé JC, Ibarretxe D, Plana N, Masana L, Monk D and Ribalta J: APOA5 genetic and epigenetic variability jointly regulate circulating triacylglycerol levels. Clin Sci (Lond). 130:2053–2059. 2016. View Article : Google Scholar : PubMed/NCBI
28	Kershaw EE, Schupp M, Guan HP, Gardner NP, Lazar MA and Flier JS: PPARgamma regulates adipose triglyceride lipase in adipocytes in vitro and in vivo. Am J Physiol Endocrinol Metab. 293:E1736–E1745. 2007. View Article : Google Scholar : PubMed/NCBI
29	Musunuru K: Atherogenic dyslipidemia: Cardiovascular risk and dietary intervention. Lipids. 45:907–914. 2010. View Article : Google Scholar : PubMed/NCBI
30	Watson JD: Type 2 diabetes as a redox disease. Lancet. 383:841–843. 2014. View Article : Google Scholar : PubMed/NCBI
31	Baldwin SJ, Clarke SE and Chenery RJ: Characterization of the cytochrome P450 enzymes involved in the in vitro metabolism of rosiglitazone. Br J Clin Pharmacol. 48:424–432. 1999. View Article : Google Scholar : PubMed/NCBI
32	Konno Y, Negishi M and Kodama S: The roles of nuclear receptors CAR and PXR in hepatic energy metabolism. Drug Metab Pharmacokinet. 23:8–13. 2008. View Article : Google Scholar : PubMed/NCBI
33	Kelder T, Verschuren L, van Ommen B, van Gool AJ and Radonjic M: Network signatures link hepatic effects of anti-diabetic interventions with systemic disease parameters. BMC Syst Biol. 8:1082014. View Article : Google Scholar : PubMed/NCBI
34	Nelson DR, Zeldin DC, Hoffman SM, Maltais LJ, Wain HM and Nebert DW: Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternative-splice variants. Pharmacogenetics. 14:1–18. 2004. View Article : Google Scholar : PubMed/NCBI
35	Ma B, Xiong X, Chen C, Li H, Xu X, Li X, Li R, Chen G, Dackor RT, Zeldin DC and Wang DW: Cardiac-specific overexpression of CYP2J2 attenuates diabetic cardiomyopathy in male streptozotocin-induced diabetic mice. Endocrinology. 154:2843–2856. 2013. View Article : Google Scholar : PubMed/NCBI
36	Panunti B and Fonseca V: Effects of PPAR gamma agonists on cardiovascular function in obese, non-diabetic patients. Vascul Pharmacol. 45:29–35. 2006. View Article : Google Scholar : PubMed/NCBI
37	Castro MCD and Singer BH: Controlling the false discovery rate: A new application to account for multiple and dependent tests in local statistics of spatial association. Geographical Anal. 38:180–208. 2006. View Article : Google Scholar