Changes of homocysteine metabolism key enzyme in insulin resistance rat model

doi:10.3969/j.issn.0529-1356.2013.04.016

Abstract

Abstract:

Objective To research the homocysteine change in an insulin resistance model for SD rats, and to discusse the molecular mechanism of the homocysteine change. Methods Twenty healthy rats, six weeks of age, were randomly divided into the control
group (n=10) and the insulin resistance group (n=10). Normal food was fed in control group；The insulin resistance model was established by high fat diet and gavaged by the high fat for 3 months. The concentrations of homocysteine, glucose, insulin,
total cholesterol and triglyceride were measured in the fasting state. At the same time, the insulin resistance index (ISI) was calculated. The expressions of methylenetetrahydrofolate reductase (MTHFR), cystathionine β synthase (CBS) and methionine
synthetase (MTR) were detected by immunohistochemistry, RT-PCR and Western blotting in the rat liver tissue. Results The concentrations of the blood glucose and blood insulin in the insulin resistance group were higher than that in the control group (P<0.05)，
the insulin resistance index was increased, so the insulin resistance model was successed. The concentrations of triglyceride and homocysteine were increased (P<0.05). However, the concentration of the total cholesterol was no statistical significance
(P>0.05). The protein and mRNA expressions of MTHER and CBS in insulin resistance group were lower compared with the control group by RTPCR, Western blotting and immunohistochemical staining(P<0.05). However, the expression of MTR protein and mRNA
were not different between the insulin resistance group and the control group (P>0.05). Conclusion The homocysteine concentration is higher in the condition of insulin resistance, which may be related to decrease with the expression of MTHER and CBS in metabolic
transformation of homocysteine.

Key words: Insulin resistance, Homocysteine, Methylenetetrahydrofolate reductase, Cystathionine &beta, synthase, Methionine synthetase, Immunohistochemistry, Western blotting, RT-PCR, Rat 

FAN Xiao-ming GUO Jia-zhi LIU Shi-chang ZHANG Tie-jun KANG Li LU Di GUI Li* LI Shu-de*. Changes of homocysteine metabolism key enzyme in insulin resistance rat model[J]. AAS, 2013, 44(4 ): 530-534.

References

［1］Oliver E, McGillicuddy F, Phillips C, et al. The role of inflammation and macrophage accumulation in the development ofobesity-induced type 2 diabetes mellitus and the possible therapeutic effects of long-chain n-3 PUFA［J］. Proc Nutr Soc, 2010, 69(2): 232-243.
［2］Vayá A, Rivera L, Hernández-Mijares A, et al. Homocysteine levels in morbidly obese patients. Its association with waist circumference and insulin resistance［J］. Clin Hemorheol Microcirc, 2012, 52(1):49-56.
［3］Uysal O, Arikan E, Cakir B. Plasma total homocysteine level and its association with carotid intima-media thickness in obesity［J］. J Endocrinol Invest, 2005, 28 (10):928-934.
［4］Masaki T, Anan F, Anai M, et al. Hyperhomocysteinemia is associated with visceral adiposity in Japanese patients with type 2 diabetes mellitus［J］. Diabetes Res Clin Pract, 2007, 77(2): 168-173.
［5］Ebesunun MO, Obajobi EO. Elevated plasma homocysteine in type 2 diabetes mellitus: a risk factor for cardiovascular diseases［J］. Pan Afr Med J, 2012, 12:48.
［6］Huang T, Asimi S, Lou D, et al. Plasma phospholipid polyunsaturated fatty acids and homocysteine in Chinese type 2 diabetes patients［J］. Asia Pac J Clin Nutr, 2012, 21(3):394-399.
［7］Wang JX, Li XJ, Liu YH, et al. Comparison of high fat and/or high sugar-induced hepatic insulin resistance in rats［J］. China Pharmacist, 2012, 15(6): 747-750.（in Chinese)
     王俊贤, 李小军, 刘跃辉, 等. 高糖、高脂诱导大鼠肝脏胰岛素抵抗评价［J］. 中国药师, 2012, 15(6): 747-750.
［8］Zhou X, Han DW, Li SH, et al. The research of high sugar and high fat induced non-alcoholic fatty liver disease (NAFLD) and hyperglycemia animal model［J］. Chinese Journal of Comparative Medicine, 2011, 21(7):22-27.(in Chinese)
     周鑫, 韩德五, 李素红, 等. 高糖高脂致大鼠非酒精性脂肪肝合并高血糖动物模型的研究［J］. 中国比较医学杂志, 2011, 21(7):22-27.
［9］Gu Y, Wang X, Li ShD,et al. Effect of homocysteine on PDK1 in skeletal muscle tissue of mice［J］. Journal of Kunming Medical University, 2012, 33(2): 40-44.(in Chinese)
     顾玉，王昕，李树德，等. 同型半胱氨酸对骨骼肌组织PDK1的影响［J］. 昆明医学院学报，2012, 33(2): 40-44. 
［10］Wang YN, Gu Y, Li ShD, et al. Effect of homocysteine on the expression and distribution of GLUT4 in skeletal muscle cells［J］. Journal of Kunming Medical University, 2012, 33(1): 16-19.（in Chinese)
      王雅楠, 顾玉, 李树德，等. 同型半胱氨酸对骨骼肌细胞GLUT4表达和分布的影响［J］. 昆明医学院学报, 2012, 33（1）: 16-19.
［11］Yang GQ, Lu JM, Liu HF, et al. The impact of pioglitazone on plasma homocysteine high fat diet induced insulin resistancein rats［J］. Zhonghua Nei Ke Za Zhi, 2005, 44(1):38-41.
［12］Fonseca VA, Mudaliar S, Schmdt B, et al. Plasma homocysteine concentraction are regulated by acute hyperinsulinemia in momdi-abetic but not type 2 diabetic subjects［J］. Metabolism, 1998, 47(6): 686-689.
［13］Liu Y, Liu YQ, Morita T, et al. Effect of dietary supplementation with folate on choline deficiency-induced hyperhomocysteinemia in rats［J］. J Nutr Sci Vitaminol, 2012, 58(1): 20-28.
［14］Baron H, KidromM, Fried lander Y, et al. Plasma total homocysteine levels in subjects with hyperinsulinemia［J］. J Intern Med, 2000, 247(2): 287-294.
［15］Sariman N, Levent E, Aksungar FB, et al. Homocysteine levels and echocardio-graphic findings in obstructive sleep apnea syndrome［J］. Respiration, 2010, 79 (1):38-45.
［16］Dicker-Brown A, Fonseca VA, Fink LM, et al. The effect of glucose and insulin on the activity of methylenetet rahydrofolatereductase and cystathionine beta synthase: studies in hepatocytes［J］. Atherosclerosis, 2001, 158(2): 297-301.
［17］Poirier LA, Brown AT, Fink LM, et al. Blood S-adenosylmethionine concentrations and lymphocyte methylenetetrahydrofolate reductase activity in diabetes mellitus and diabetic nephropathy［J］. Metabolism, 2001, 50(9): 1014-1018.
［18］Setola E, Monti LD, Galluccio E, et al. Insulin resistance and endothelial function are improved after folate and vitamin B12 therapy in patients with metabolic syndrome: relationship between homocysteine levels and hyperinsulinemia［J］. Eur J Endocrinol, 2004, 151(4): 483-489.

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