Assessment of serum arginase I as a type 2 diabetes mellitus diagnosis biomarker in patients

Wang,Song; Fang,Fang; Jin,Wen‑Bo; Wang,Xia; Zheng,Da‑Wei

doi:10.3892/etm.2014.1768

August-2014 Volume 8 Issue 2

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

August-2014 Volume 8 Issue 2

Full Size Image

Article

Assessment of serum arginase I as a type 2 diabetes mellitus diagnosis biomarker in patients

Authors:
- Song Wang
- Fang Fang
- Wen‑Bo Jin
- Xia Wang
- Da‑Wei Zheng
View Affiliations / Copyright

Affiliations: Department of Endocrinology, Henan Nanyang Central Hospital, Nanyang, Henan 473000, P.R. China, Department of Computed Tomography, Henan Nanyang Central Hospital, Nanyang, Henan 473000, P.R. China, Department of Nursing, Henan Nanyang Central Hospital, Nanyang, Henan 473000, P.R. China, Department of Respiratory Medicine, Henan Nanyang Central Hospital, Nanyang, Henan 473000, P.R. China
Pages: 585-590
|
Published online on: June 6, 2014

https://doi.org/10.3892/etm.2014.1768
Expand metrics +

Abstract

Previous studies have reported that levels of serum arginase I are increased in certain diseases. However, the exact association between arginase I and diabetes mellitus (DM) has yet to be determined. The aim of the present study was to investigate the correlation between arginase I activity and DM to determine whether arginase I activity may be used as a diagnostic biomarker for DM. DM was induced by a streptozotocin injection, while the arginase inhibitor, citrulline, was administered daily. Serum levels of glucose, reactive oxygen species (ROS) and arginase I activity were analyzed, and quantitative polymerase chain reaction and western blot analysis were performed to detect the mRNA and protein expression levels of arginase I, respectively. In addition, western blot analysis was used to determine the protein expression of the Tie 2 receptor. Pearson's analysis was used to determine the correlation between arginase I activity and Tie 2 expression, while concordance analysis was performed using the Cohen's test to obtain the Kappa statistic. The results demonstrated that serum arginase I activity levels in the rats with DM were significantly elevated compared with the control group, and positively correlated with the blood glucose levels. In addition, the blood glucose and ROS levels were increased significantly in the rats with DM. Arginase I mRNA and protein expression levels were significantly elevated in the diabetic rats when compared with the control group, and Tie 2 expression levels increased and were shown to correlate with arginase I activity in the diabetic rats. In addition, arginase I activity was shown to correlate with glucose intolerance and post‑load glucose values. Good concordance was observed between arginase I activity and the clinical diagnosis for DM (κ=0.876; P<0.001). Therefore, the results indicated that arginase I may function as a diagnostic biomarker for DM rats model.

View Figures

View References

1	Shen K, Ji Y, Chen GQ, Huang B, Zhang X, Wu S, Yu GP and Wang XC: Expression and clinical significance of the NDA repair enzyme MYH in esophageal squamous cell carcinoma. Exp Ther Med. 2:1117–1120. 2011.PubMed/NCBI
2	Cederbaum SD, Yu H, Grody WW, Kern RM, Yoo P and Iyer RK: Arginases I and II: do their functions overlap? Mol Genet Metab. 81(Suppl 1): S38–S44. 2004. View Article : Google Scholar : PubMed/NCBI
3	Jenkinson CP, Grody WW and Cederbaum SD: Comparative properties of arginase. Comp Biochem Physiol B Biochem Mol Biol. 114:107–132. 1996. View Article : Google Scholar
4	Na S, Kim OS, Ryoo S, Kweon TD, Choi YS, Shim HS and Oh YJ: Cervical ganglion block attenuates the progression of pulmonary hypertension via nitric oxide and arginase pathways. Hypertension. 63:309–315. 2014. View Article : Google Scholar : PubMed/NCBI
5	Yang J, Gonon AT, Sjöquist PO, Lundberg JO and Pernow J: Arginase regulates red blood cell nitric oxide synthase and export of cardioprotective nitric oxide bioactivity. Proc Natl Acad Sci USA. 110:15049–15054. 2013. View Article : Google Scholar : PubMed/NCBI
6	Maarsingh H, Zaagsma J and Meurs H: Arginase: a key enzyme in the pathophysiology of allergic asthma opening novel therapeutic perspectives. Br J Pharmacol. 158:652–664. 2009. View Article : Google Scholar : PubMed/NCBI
7	Munder M: Arginase: an emerging key player in the mammalian immune system. Br J Pharmacol. 158:638–651. 2009. View Article : Google Scholar : PubMed/NCBI
8	Liu JF, Du ZD, Chen Z, Han ZC and He ZX: Granulocyte colony-stimulating factor attenuates monocrotaline-induced pulmonary hypertension by upregulating endothelial progenitor cells via the nitric oxide system. Exp Ther Med. 6:1402–1408. 2013.
9	Bekpinar S, Gurdol F, Unlucerci Y, Develi S and Yilmaz A: Serum levels of arginase I are associated with left ventricular function after myocardial infarction. Clin Biochem. 44:1090–1093. 2011. View Article : Google Scholar : PubMed/NCBI
10	Zimmet P, Alberti KG and Shaw J: Global and societal implications of the diabetes epidemic. Nature. 414:782–787. 2001. View Article : Google Scholar : PubMed/NCBI
11	Hoeldtke RD, Bryner KD, McNeill DR, Warehime SS, Van Dyke K and Hobbs G: Oxidative stress and insulin requirements in patients with recent-onset type I diabetes. J Clin Endocrinol Metab. 88:1624–1628. 2003. View Article : Google Scholar : PubMed/NCBI
12	Taysi S, Polat F, Gul M, Sari RA and Bakan E: Lipid peroxidation, some extracullar antioxidant enzymes in serum of patients with rheumatoid arthritis. Rheumatol Int. 21:200–204. 2002. View Article : Google Scholar : PubMed/NCBI
13	Wu G and Meininger CJ: Arginine nutrition and cardiovascular function. J Nutr. 130:2626–2629. 2000.PubMed/NCBI
14	Fiorentino TV, Prioletta A, Zuo P and Folli F: Hyperglycemia-induced oxidative stress and its role in diabetes mellitus related cardiovascular diseases. Curr Pharm Des. 19:5695–5703. 2013. View Article : Google Scholar : PubMed/NCBI
15	Bjelakovic G, Sokolovic D, Ljiljana S, Kocic G, Jevtovic T, Stojanovic I, IIic M, Bjelakovic LJ, Zivic S, Pavlovic D, Nikolić J and Basic J: Arginase activity and magnesium levels in blood of children with diabetes mellitus. J Basic Clin Physiol Pharmacol. 20:319–334. 2009. View Article : Google Scholar : PubMed/NCBI
16	Teerlink T: Determination of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine in biological sample by HPLC. Methods Mol Med. 108:263–274. 2005.PubMed/NCBI
17	Newaskar M, Hardy KA and Morris CR: Asthma in sickle cell disease. Scientific World Journal. 11:1138–1152. 2011. View Article : Google Scholar : PubMed/NCBI
18	Narayanan SP, Rojas M, Suwanpradid J, Toque HA, Caldwell RW and Caldwell RB: Arginase in retinopathy. Prog Retin Eye Res. 36:260–280. 2013. View Article : Google Scholar : PubMed/NCBI
19	Pernow J and Jung C: Arginase as a potential target in the treatment of cardiovascular disease: reversal of arginine steal? Cardiovasc Res. 98:334–343. 2013. View Article : Google Scholar : PubMed/NCBI
20	Kang ES, Ford K, Grokulsky G, Wang YB, Chiang TM and Acchiardo SR: Normal circulating adult human red blood cells contain inactive NOS proteins. J Lab Clin Med. 135:444–451. 2000. View Article : Google Scholar : PubMed/NCBI
21	Morris CR, Poljakovic M, Lavrisha L, Machado L, Kuypers FA and Morris SM Jr: Decreased arginine bioavailability and increased serum arginase activity in asthma. Am J Respir Crit Care Med. 170:148–153. 2004. View Article : Google Scholar : PubMed/NCBI
22	Giri H, Chandel S, Dwarakanath LS, Sooriyakala S and Dixit M: Increased endothelial inflammation, sTie-2 and arginase activity in umbilical cords obtained from gestational diabetic mothers. PLoS One. 8:e845462013. View Article : Google Scholar : PubMed/NCBI
23	Ramírez-Zamora S, Méndez-Rodríguez ML, Olguín-Martínez M, Sánchez-Sevilla L, Quintana-Quintana M, García-García N and Hernández-Muñoz R: Increased erythrocytes by-products of arginine catabolism are associated with hyperglycemia and could be involved in the pathogenesis of type 2 diabetes mellitus. PLoS One. 8:e668232013.PubMed/NCBI
24	Wei J, Tang Q, Liu L and Bin J: Combination of peroxisome proliferator-activated receptor α/γ agonists may benefit type 2 diabetes patients with coronary disease through inhibition of inflammatory cytokine secretion. Exp Ther Med. 5:783–788. 2013.
25	Griesmacher A, Kindhauser M, Andert SE, Schreiner W, Toma C, Knoebl P, Pietschmann P, Prager R, Schnack C, Schernthaner G, et al: Enhanced serum levels of thiobarbituric-acid-reactive substances in diabetes mellitus. Am J Med. 98:469–475. 1995. View Article : Google Scholar : PubMed/NCBI
26	Xin G, Du J, Wang YT and Liang TT: Effect of oxidative stress on heme oxygenase-1 expression in patients with gestational diabetes mellitus. Exp Ther Med. 7:478–482. 2014.PubMed/NCBI
27	Yao L, Chandra S, Toque HA, Bhatta A, Rojas M, Caldwell RB and Caldwell RW: Prevention of diabetes-induced arginase activation and vascular dysfunction by Rho kinase (ROCK) knockout. Cardiovasc Res. 97:509–519. 2013. View Article : Google Scholar : PubMed/NCBI
28	Elms SC, Toque HA, Rojas M, Xu Z, Caldwell RW and Caldwell RB: The role of arginase I in diabetes-induced retinal vascular dysfunction in mouse and rat models of diabetes. Diabetologia. 56:654–662. 2013. View Article : Google Scholar : PubMed/NCBI
29	Findley CM, Cudmore MJ, Ahmed A and Kontos CD: VEGF induces Tie 2 shedding via a phosphoinositide 3-kinase/Akt dependent pathway to modulate Tie 2 signaling. Arterioscler Thromb Vasc Biol. 27:2619–2626. 2007. View Article : Google Scholar : PubMed/NCBI
30	Onimaru M, Yonemitsu Y, Suzuki H, Fujii T and Sueishi K: An autocrine linkage between matrix metalloproteinase-14 and Tie 2 via ectodomain shedding modulates angiopoietin-1-dependent function in endothelial cells. Arterioscler Thromb Vasc Biol. 30:818–826. 2010. View Article : Google Scholar
31	Buhimschi CS, Bhandari V, Dulay AT, Thung S, Rzaeq SS, et al: Amniotic fluid angiopoietin-1, angiopoietin-2, and soluble receptor tunica interna endothelial cell kinase-2 levels and regulation in normal pregnancy and intraamniotic inflammation-induced pretern birth. J Clin Endocrinol Metab. 95:3428–3436. 2010. View Article : Google Scholar
32	Sarikaphuti A, Nararatwanchai T, Hashiguchi T, Ito T, Thaworanunta S, Kikuchi K, Oyama Y, Maruyama I and Tancharoen S: Preventive effects of Morus alba L. anthocyanins on diabetes in Zucker diabetic fatty rats. Exp Ther Med. 6:689–695. 2013.