1.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
Journal of Huazhong University of Science and Technology (Medical Sciences) 2011;31(3):306-11
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.
2.Reduction of insulin resistance in HepG2 cells by knockdown of LITAF expression in human THP-1 macrophages.
Yan, HUANG ; Jie, LIU ; Yancheng, XU ; Zhe, DAI ; Martins Hedson, ALVES
Journal of Huazhong University of Science and Technology (Medical Sciences) 2012;32(1):53-8
The molecular mechanism by which obesity induces insulin resistance is not completely understood. The aim of this study was to determine how lipopolysaccharide-induced tumor necrosis-α factor (LITAF) influenced obesity-induced insulin resistance using a cellular co-culture system. The cells were divided into 3 groups: palmitic acid (PA) stimulation group, LITAF small interfering RNA (siRNA) group and untreated (NC) group. The LITAF siRNA was used for knockdown of LITAF expression in human THP-1 macrophages. The expression levels of LITAF, IRS-2, IRS-2Tyr465, PI3K, and GLUT2 in each group were measured by using quantitative reverse transcriptase real-time polymerase chain reaction and Western blotting. The expression of LITAF was much higher in the PA group than in the siRNA and NC groups (*P<0.05); meanwhile, the expression of IRS-2, IRS-2Tyr465, PI3K, and GLUT2 was much lower in the PA group than in the NC group (*P<0.05); however, IRS-2, IRS-2Tyr465, PI3K, and GLUT2 had much higher expression in the siRNA group than in the PA group (*P<0.05). It is concluded that PA can induce insulin resistance in liver cells and knockdown of LITAF expression can reduce insulin resistance in liver cells, suggesting LITAF may regulate the insulin signal transduction pathway involved in obesity-induced insulin resistance.
3.Association of SUMO4 Met55Val Variation with Increased Insulin Resistance in Newly Diagnosed Type 2 Diabetes in a Chinese Population
JI ZHENZHONG ; DAI ZHE ; HUANG YAN ; Martins Alves HEDSON ; XU YANCHENG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2011;31(3):306-311
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 βcell 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 SUMO4Met55Val variant was associated with increased insulin resistance in Chinese patients with newly diagnosed type 2 diabetes.
4.Reduction of Insulin Resistance in HepG2 Cells by Knockdown of LITAF Expression in Human THP-1 Macrophages
HUANG YAN ; LIU JIE ; XU YANCHENG ; DAI ZHE ; Alves Hedson MARTINS
Journal of Huazhong University of Science and Technology (Medical Sciences) 2012;32(1):53-58
The molecular mechanism by which obesity induces insulin resistance is not completely understood.The aim of this study was to determine how lipopolysaccharide-induced tumor necrosis-α factor (LITAF) influenced obesity-induced insulin resistance using a cellular co-culture system.The cells were divided into 3 groups:palmitic acid (PA) stimulation group,LITAF small interfering RNA (siRNA) group and untreated (NC) group.The LITAF siRNA was used for knockdown of LITAF expression in human THP-1 macrophages.The expression levels of LITAF,IRS-2,IRS-2Tyr465,PI3K,and GLUT2 in each group were measured by using quantitative reverse transcriptase real-time polymerase chain reaction and Western blotting.The expression of LITAF was much higher in the PA group than in the siRNA and NC groups (*P<0.05); meanwhile,the expression of IRS-2,IRS-2Tyr465,PI3K,and GLUT2 was much lower in the PA group than in the NC group (*P<0.05); however,IRS-2,IRS-2Tyr465,PI3K,and GLUT2 had much higher expression in the siRNA group than in the PA group (*P<0.05).It is concluded that PA can induce insulin resistance in liver cells and knockdown of LITAF expression can reduce insulin resistance in liver cells,suggesting LITAF may regulate the insulin signal transduction pathway involved in obesity-induced insulin resistance.