Association of SUMO4 Met55Val variation with increased insulin resistance in newly diagnosed type 2 diabetes in a Chinese population

Zhenzhong Ji , Zhe Dai , Yan Huang , Hedson Alves Martins , Yancheng Xu

Current Medical Science ›› 2011, Vol. 31 ›› Issue (3) : 306 -311.

PDF
Current Medical Science ›› 2011, Vol. 31 ›› Issue (3) : 306 -311. DOI: 10.1007/s11596-011-0372-9
Article

Association of SUMO4 Met55Val variation with increased insulin resistance in newly diagnosed type 2 diabetes in a Chinese population

Author information +
History +
PDF

Abstract

SUMO4 Met55Val variation was shown to be related to type 2 diabetes susceptibility and the vascular complications in Asian people. To further examine the related mechanisms, this study was designed to evaluate the association of SUMO4 Met55Val polymorphism with insulin resistance and β cell function in newly diagnosed type 2 diabetic patients in a Chinese population. Four hundred and twenty seven newly diagnosed type 2 diabetic patients were selected for SUMO4 Met55Val polymorphism genotype analysis. All subjects underwent a 75-g oral glucose tolerance test (OGTT) to estimate the insulin sensitivity and β cell function. Anthropometrics and a metabolic profile were used for phenotyping analysis. The results showed that the SUMO4 Met55Val polymorphism was associated with higher insulin resistance (P<0.001) and lower insulin sensitivity (P<0.001). Patients with GG genotype had higher levels of plasma glucose, insulin and C peptide. Insulin sensitivity index (ISI) was closely correlated with body mass index (BMI) in patients with GG genotype in comparison to the counterparts with AG or AA genotype (r= −0.504 vs. r= −0.430 vs. r= −0.340). Multiple regression linear analysis showed that SUMO4 Met55Val polymorphism was an independent determinant for insulin sensitivity (P=0.001), which, along with triglyceride, BMI and sex, could account for 20.1% of the variation in ISI. The result remained the same after adjusting for BMI and sex. No association was found between SUMO4 Met55Val polymorphism and β cell function (all P>0.05). It was concluded that SUMO4 Met55Val variant was associated with increased insulin resistance in Chinese patients with newly diagnosed type 2 diabetes.

Keywords

SUMO4 / type 2 diabetes / insulin resistance

Cite this article

Download citation ▾
Zhenzhong Ji, Zhe Dai, Yan Huang, Hedson Alves Martins, Yancheng Xu. Association of SUMO4 Met55Val variation with increased insulin resistance in newly diagnosed type 2 diabetes in a Chinese population. Current Medical Science, 2011, 31(3): 306-311 DOI:10.1007/s11596-011-0372-9

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

GuoD., LiM., ZhangY., et al.. A functional variant of SUMO4, a new I kappa B alpha modifier, is associated with type 1 diabetes. Nat Genet, 2004, 36(8): 837-841

[2]

ZouY.F., FengX.L., TaoJ.H., et al.. Association of SUMO4 MET55VAL polymorphism with susceptibility to autoimmune and inflammatory diseases: a meta-analysis. Int J Immunogenet, 2010, 37(5): 345-354

[3]

NosoS., IkegamiH., FujisawaT., et al.. Genetic heterogeneity in association of the SUMO4 M55V variant with susceptibility to type 1 diabetes. Diabetes, 2005, 54(12): 3582-3586

[4]

AribiM.. Candidate genes implicated in type 1 diabetes susceptibility. Curr Diabetes Rev, 2008, 4(2): 110-121

[5]

SangY., ZongW., LiuM., et al.. Association of SUMO4 M55V polymorphism with type 1 diabetes in Chinese children. J Pediatr Endocrinol Metab, 2010, 23(10): 1083-1086

[6]

NosoS., FujisawaT., KawabataY., et al.. Association of small ubiquitin-like modifier 4 (SUMO4) variant, located in IDDM5 locus, with type 2 diabetes in the Japanese population. J Clin Endocrinol Metab, 2007, 92(6): 2358-2362

[7]

ShimadaT., FurukawaY., FurutaH., et al.. SUMO4 Met55Val polymorphism is associated with coronary heart disease in Japanese type 2 diabetes individuals. Diabetes Res Clin Pract, 2009, 85(1): 85-89

[8]

LinH.Y., LiS.L., YuM.L., et al.. Small ubiquitin-like modifier-4 Met55Val polymorphism is associated with glycemic control of Type 2 diabetes mellitus in Taiwan. J Endocrinol Invest, 2010, 33(6): 401-405

[9]

LinH.Y., WangC.L., HsiaoP.J., et al.. SUMO4 MET55VAL variant is associated with diabetic nephropathy in type 2 diabetes. Diabetes, 2007, 56(4): 1177-1180

[10]

HotamisligilG.S.. Inflammation and metabolic disorders. Nature, 2006, 444(7121): 860-867

[11]

BourlierV., BouloumieA.. Role of macrophage tissue infiltration in obesity and insulin resistance. Diabetes Metab, 2009, 35(4): 251-260

[12]

FuentesL., RoszerT., RicoteM.. Inflammatory mediators and insulin resistance in obesity: role of nuclear receptor signaling in macrophages. Mediators Inflamm, 2010, 2010: 219583

[13]

HotamisligilG.S., ShargillN.S., SpiegelmanB.M.. Adipose expression of tumor necrosis factor-α: direct role in obesity-linked insulin resistance. Science, 1993, 259(5091): 87-91

[14]

HerderC., SchneitlerS., RathmannW., et al.. Low-grade inflammation, obesity, and insulin resistance in adolescents. J Clin Endocrinol Metab, 2007, 92(12): 4569-4574

[15]

BonoraE., TargherG., AlbericheM., et al.. Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity. Diabetes Care, 2001, 23(1): 57-63

[16]

MatsudaM., DeFronzoR.A.. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care, 1999, 22(9): 1462-1470

[17]

MatthewsD.R., HoskerJ.P., RudenskiA.S., et al.. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia, 1985, 28(7): 412-419

[18]

HansonR.L., PratleyR.E., BogardusC., et al.. Evaluation of simple indices of insulin sensitivity and insulin secretion for use in epidemiologic studies. Am J Epidemiol, 2000, 151(2): 190-198

[19]

CaiD., YuanM., FrantzD.F., et al.. Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB. Nat Med, 2005, 11(2): 183-190

[20]

YangJ., ParkY., ZhangH., et al.. Feed-forward signaling of TNF-alpha and NF-kappaB via IKK-beta pathway contributes to insulin resistance and coronary arteriolar dysfunction in type 2 diabetic mice. Am J Physiol Heart Circ Physiol, 2009, 296(6): H1850-1858

[21]

GaoZ., YinJ., ZhangJ., et al.. Inactivation of NF-kappaB p50 leads to insulin sensitization in liver through post-translational inhibition of p70S6K. J Biol Chem, 2009, 284(27): 18368-18376

[22]

WangC.Y., YangP., LiM., et al.. Characterization of a negative feedback network between SUMO4 expression and NFkappaB transcriptional activity. Biochem Biophys Res Commun, 2009, 381(4): 477-481

[23]

WangC.Y., SheJ.X.. SUMO4 and its role in type 1 diabetes pathogenesis. Diabetes Metab Res Rev, 2008, 24(2): 93-102

[24]

PirolaL., JohnstonA.M., Van ObberghenE.. Modulation of insulin action. Diabetologia, 2004, 47(2): 170-184

[25]

SenguptaU., UkilS., DimitrovaN., et al.. Expression-based network biology identifies alteration in key regulatory pathways of type 2 diabetes and associated risk/complications. PLoS One, 2009, 4(12): e8100

[26]

WeiW., YangP., PangJ., et al.. A stress-dependent SUMO4 sumoylation of its substrate proteins. Biochem Biophys Res Commun, 2008, 375(3): 454-4592

AI Summary AI Mindmap
PDF

89

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/