Objectives To analyze the relationship between homocysteine (Hcy) and insulin resistance in rats with intrauterine growth restriction,to discuss the possibility of affecting Hcy level by changing early diet,therely influencing insulin sensitivity,and to explore possible molecular mechanisms. Methods 1)The model of intrauterine growth retardation(IUGR) rats was established by low-protein and caloric restriction in the second and third trimester of pregnancy.IUGR newborn pups were randomly divided into dietary intervention group and non-intervention group.Lactating female rats of dietary intervention group were fed with high folate and vitamin B12. Lactating female rats of non-intervention group were fed with normal diet.All of newborn pups were weaned on the 21st day after birth and then fed with normal diet to 120 days.2)On the 120th day after birth,fasting plasma gluoose(FPG),fasting insulin (FINS)and Hcy of the rats in three groups were measured.Insulin resistance index(IRI) were calculated to evaluate insulin sensitivity.The relationship between Hcy and IRI was disscussed.3)On the 120th day after birth,skeletal muscle tissues were collected from rats of the three groups,phosphatidylinositol 3-kinase(PI3K) and phosphatase and tension homologuedeleted on chromosome 10(PTEN)protein expression levels in phosphatidyl inositol 3-kinse /protein kinase B (PI3K/AKT) insulin signaling pathway were determined by using western blotting.The relationship between Hcy and protein expression was disscussed. Results 1)On the 120th day,FPG,FINS,IRI and Hcy levels in dietary intervention group were significantly lower than those in non-intervention group,but were higher than those in control group (P<0.05).2)The Hcy level of the three groups was highly positively correlated with IRI (r=0.937,P<0.05).3)On the 120th day,Hcy was negatively correlated with PI3K protein expression(r=-0.88) and positively correlated with PTEN protein expression(r=0.85) in IUGR rats,both of which were statistically significant (P<0.05). Conclusions Maternal lactation can serve as a window period for early postnatal nutrition intervention.Supplementation with folic acid and vitamin B12 can reduce the Hcy level of IUGR offspring Meawhite,Hcy level is highly positively correlated with insulin resistance,and the change of Hcy is closely related to the expression of key molecules in the PI3K/AKT insulin signaling pathway in the skeletal muscle of IUGR offspring.
Key words
homocysteine /
intrauterine growth retardation /
insulin resistance /
PI3K/AKT signaling pathway
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References
[1] Hu Y,Xu Y,Wang G.Homocysteine levels are associated with endothelial function in newly diagnosed type 2 diabetes mellitus patients[J].Metab Syndr Relat Disord,2019,17(6):323-327.
[2] Tessari P,Cecchet D,Vettore M,et al.Decreased homocysteine trans-sulfuration in hypertension with hyperhomocysteinemia:relationship with insulin resistance[J].J Clin Endocrinol Metab,2018,103(1):56-63.
[3] 张慧,王新利,张金,等.叶酸和维生素B12对胎儿生长受限大鼠胰岛素抵抗的影响[J].中华围产医学杂志,2015,18(8):568-572.
[4] 张慧,王新利,张金,等.叶酸和维生素B12对宫内生长受限大鼠骨骼肌磷脂酰肌醇3激酶表达的影响[J].中国儿童保健杂志,2018,26(1):32-36.
[5] 李海燕,郁金芬,许洁,等.妊娠期糖尿病胰岛素抵抗与同型半胱氨酸水平的相关性[J].中国热带医学,2017,17(12):1243-1246.
[6] 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.
[7] Liu P,Huang J,Zhong L.Role and mechanism of homocysteine in affecting hepatic protein-tyrosine phosphatase 1B[J].BBA-General Subjects,2019,1863(5):941-949.
[8] Santilli F,Davi G,Patrono C.Homocysteine,methylenetetra-hydrofolate reductase,folate status and atherothrombosis:a mechanistic and clinical perspective[J].Vascul Pharmacol,2016,78:1-9.
[9] Wierzbicki AS.Homocysteine and cardiovascular disease:a review of the evidence[J].Diab Vasc Dis Res,2007,4(2):143-150.
[10] Kaur G,Gaur R,Yadav S,et al.Association of vitamin B12 mediated hyperhomocysteinemia and methylenetetrafolate reductase(C677T) gene polymorphism with cognitive impairment:a population based study from North India[J].Psychiatry Res,2018,270:123-125.
[11] Yeh EL,Huang YC,Tsai SF,et al.Relationship between plasma levels of homocysteine and the related B vitamins in patients with hemodialysis adequacy or inadequacy[J].Nutrition,2018,53:103-108.
[12] Kuwahara K,Nanri A,Pham NM,et al.Serum vitamin B6,folate,and homocysteine concentrations and oxidative DNA damage in Japanese men and women[J].Nutrition,2013,29(10):1219-1223.
[13] Ni J,Zhang L,Zhou T,et al.Association between the MTH-FR C677T polymorphism,blood folate and vitamin B12 deficiency,and elevated serum total homocysteine in healthy individuals in Yunnan Province,China[J].J Chin Med Assoc,2017,80(3):147-153.
[14] Najib S,Sánchez-Margalet V.Homocysteine thiolactone inhibits insulin signaling,and glutathione has a protective effect[J].J Mol Endocrinol,2001,27(1):85-91.
[15] Stiles B,Wang Y,Stahl A,et al.Liver-specific deletion of negative regulator Pten results in fatty liver and insulin hypersensitivity[J].Proc Natl Acad Sci USA,2004,101(7):2082-2087.
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