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Start Over Author "Zhang, Zhongyang" Topic insulin resistance
5 results on '"Zhang, Zhongyang"'

1. Genome-Wide Association Study of the Modified Stumvoll Insulin Sensitivity Index Identifies BCL2 and FAM19A2 as Novel Insulin Sensitivity Loci.

Author

Walford GA, Gustafsson S, Rybin D, Stančáková A, Chen H, Liu CT, Hong J, Jensen RA, Rice K, Morris AP, Mägi R, Tönjes A, Prokopenko I, Kleber ME, Delgado G, Silbernagel G, Jackson AU, Appel EV, Grarup N, Lewis JP, Montasser ME, Landenvall C, Staiger H, Luan J, Frayling TM, Weedon MN, Xie W, Morcillo S, Martínez-Larrad MT, Biggs ML, Chen YD, Corbaton-Anchuelo A, Færch K, Gómez-Zumaquero JM, Goodarzi MO, Kizer JR, Koistinen HA, Leong A, Lind L, Lindgren C, Machicao F, Manning AK, Martín-Núñez GM, Rojo-Martínez G, Rotter JI, Siscovick DS, Zmuda JM, Zhang Z, Serrano-Rios M, Smith U, Soriguer F, Hansen T, Jørgensen TJ, Linnenberg A, Pedersen O, Walker M, Langenberg C, Scott RA, Wareham NJ, Fritsche A, Häring HU, Stefan N, Groop L, O'Connell JR, Boehnke M, Bergman RN, Collins FS, Mohlke KL, Tuomilehto J, März W, Kovacs P, Stumvoll M, Psaty BM, Kuusisto J, Laakso M, Meigs JB, Dupuis J, Ingelsson E, and Florez JC

Subjects
Chemokines, CC physiology, Female, Genetic Predisposition to Disease genetics, Humans, Insulin Receptor Substrate Proteins genetics, Insulin Receptor Substrate Proteins physiology, Male, Polymorphism, Single Nucleotide genetics, Proto-Oncogene Proteins c-bcl-2 physiology, Chemokines, CC genetics, Genome-Wide Association Study methods, Insulin Resistance genetics, Proto-Oncogene Proteins c-bcl-2 genetics
Abstract

Genome-wide association studies (GWAS) have found few common variants that influence fasting measures of insulin sensitivity. We hypothesized that a GWAS of an integrated assessment of fasting and dynamic measures of insulin sensitivity would detect novel common variants. We performed a GWAS of the modified Stumvoll Insulin Sensitivity Index (ISI) within the Meta-Analyses of Glucose and Insulin-Related Traits Consortium. Discovery for genetic association was performed in 16,753 individuals, and replication was attempted for the 23 most significant novel loci in 13,354 independent individuals. Association with ISI was tested in models adjusted for age, sex, and BMI and in a model analyzing the combined influence of the genotype effect adjusted for BMI and the interaction effect between the genotype and BMI on ISI (model 3). In model 3, three variants reached genome-wide significance: rs13422522 (NYAP2; P = 8.87 × 10(-11)), rs12454712 (BCL2; P = 2.7 × 10(-8)), and rs10506418 (FAM19A2; P = 1.9 × 10(-8)). The association at NYAP2 was eliminated by conditioning on the known IRS1 insulin sensitivity locus; the BCL2 and FAM19A2 associations were independent of known cardiometabolic loci. In conclusion, we identified two novel loci and replicated known variants associated with insulin sensitivity. Further studies are needed to clarify the causal variant and function at the BCL2 and FAM19A2 loci., (© 2016 by the American Diabetes Association.)

Published
2016
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2. Identification and validation of N-acetyltransferase 2 as an insulin sensitivity gene.

Author

Knowles JW, Xie W, Zhang Z, Chennamsetty I, Assimes TL, Paananen J, Hansson O, Pankow J, Goodarzi MO, Carcamo-Orive I, Morris AP, Chen YD, Mäkinen VP, Ganna A, Mahajan A, Guo X, Abbasi F, Greenawalt DM, Lum P, Molony C, Lind L, Lindgren C, Raffel LJ, Tsao PS, Schadt EE, Rotter JI, Sinaiko A, Reaven G, Yang X, Hsiung CA, Groop L, Cordell HJ, Laakso M, Hao K, Ingelsson E, Frayling TM, Weedon MN, Walker M, and Quertermous T

Subjects
3T3-L1 Cells, Adipogenesis drug effects, Adipogenesis physiology, Adolescent, Adult, Animals, Arylamine N-Acetyltransferase deficiency, Arylamine N-Acetyltransferase genetics, Asian People genetics, Child, Coronary Disease enzymology, Coronary Disease genetics, Europe epidemiology, Female, Gene Frequency, Genome-Wide Association Study, Glucose metabolism, Glycated Hemoglobin analysis, Hispanic or Latino genetics, Humans, Hyperglycemia enzymology, Hyperglycemia genetics, Hypertriglyceridemia enzymology, Hypertriglyceridemia genetics, Isoenzymes deficiency, Isoenzymes physiology, Lipolysis drug effects, Lipolysis physiology, Male, Mice, Mice, Knockout, Middle Aged, Polymorphism, Single Nucleotide, Prospective Studies, Taiwan epidemiology, United States epidemiology, White People genetics, Young Adult, Arylamine N-Acetyltransferase physiology, Insulin Resistance physiology, Mutation, Missense, Point Mutation
Abstract

Decreased insulin sensitivity, also referred to as insulin resistance (IR), is a fundamental abnormality in patients with type 2 diabetes and a risk factor for cardiovascular disease. While IR predisposition is heritable, the genetic basis remains largely unknown. The GENEticS of Insulin Sensitivity consortium conducted a genome-wide association study (GWAS) for direct measures of insulin sensitivity, such as euglycemic clamp or insulin suppression test, in 2,764 European individuals, with replication in an additional 2,860 individuals. The presence of a nonsynonymous variant of N-acetyltransferase 2 (NAT2) [rs1208 (803A>G, K268R)] was strongly associated with decreased insulin sensitivity that was independent of BMI. The rs1208 "A" allele was nominally associated with IR-related traits, including increased fasting glucose, hemoglobin A1C, total and LDL cholesterol, triglycerides, and coronary artery disease. NAT2 acetylates arylamine and hydrazine drugs and carcinogens, but predicted acetylator NAT2 phenotypes were not associated with insulin sensitivity. In a murine adipocyte cell line, silencing of NAT2 ortholog Nat1 decreased insulin-mediated glucose uptake, increased basal and isoproterenol-stimulated lipolysis, and decreased adipocyte differentiation, while Nat1 overexpression produced opposite effects. Nat1-deficient mice had elevations in fasting blood glucose, insulin, and triglycerides and decreased insulin sensitivity, as measured by glucose and insulin tolerance tests, with intermediate effects in Nat1 heterozygote mice. Our results support a role for NAT2 in insulin sensitivity.

Published
2015
Full Text
View/download PDF

3. Identification and validation of N-acetyltransferase 2 as an insulin sensitivity gene

Author

Knowles, Joshua W, Xie, Weijia, Zhang, Zhongyang, Chennamsetty, Indumathi, Assimes, Themistocles L, Paananen, Jussi, Hansson, Ola, Pankow, James, Goodarzi, Mark O, Carcamo-Orive, Ivan, Morris, Andrew P, Chen, Yii-Der I, Mäkinen, Ville-Petteri, Ganna, Andrea, Mahajan, Anubha, Guo, Xiuqing, Abbasi, Fahim, Greenawalt, Danielle M, Lum, Pek, Molony, Cliona, Lind, Lars, Lindgren, Cecilia, Raffel, Leslie J, Tsao, Philip S, Schadt, Eric E, Rotter, Jerome I, Sinaiko, Alan, Reaven, Gerald, Yang, Xia, Hsiung, Chao A, Groop, Leif, Cordell, Heather J, Laakso, Markku, Hao, Ke, Ingelsson, Erik, Frayling, Timothy M, Weedon, Michael N, Walker, Mark, and Quertermous, Thomas

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Health Sciences, Genetics, Diabetes, Human Genome, Cardiovascular, Prevention, Obesity, 2.1 Biological and endogenous factors, Metabolic and endocrine, 3T3-L1 Cells, Adipogenesis, Adolescent, Adult, Animals, Arylamine N-Acetyltransferase, Asian People, Child, Coronary Disease, Europe, Female, Gene Frequency, Genome-Wide Association Study, Glucose, Glycated Hemoglobin, Hispanic or Latino, Humans, Hyperglycemia, Hypertriglyceridemia, Insulin Resistance, Isoenzymes, Lipolysis, Male, Mice, Mice, Knockout, Middle Aged, Mutation, Missense, Point Mutation, Polymorphism, Single Nucleotide, Prospective Studies, Taiwan, United States, White People, Young Adult, RISC (Relationship between Insulin Sensitivity and Cardiovascular Disease) Consortium, EUGENE2 (European Network on Functional Genomics of Type 2 Diabetes) Study, GUARDIAN (Genetics UndeRlying DIAbetes in HispaNics) Consortium, SAPPHIRe (Stanford Asian and Pacific Program for Hypertension and Insulin Resistance) Study, Medical and Health Sciences, Immunology, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Decreased insulin sensitivity, also referred to as insulin resistance (IR), is a fundamental abnormality in patients with type 2 diabetes and a risk factor for cardiovascular disease. While IR predisposition is heritable, the genetic basis remains largely unknown. The GENEticS of Insulin Sensitivity consortium conducted a genome-wide association study (GWAS) for direct measures of insulin sensitivity, such as euglycemic clamp or insulin suppression test, in 2,764 European individuals, with replication in an additional 2,860 individuals. The presence of a nonsynonymous variant of N-acetyltransferase 2 (NAT2) [rs1208 (803A>G, K268R)] was strongly associated with decreased insulin sensitivity that was independent of BMI. The rs1208 "A" allele was nominally associated with IR-related traits, including increased fasting glucose, hemoglobin A1C, total and LDL cholesterol, triglycerides, and coronary artery disease. NAT2 acetylates arylamine and hydrazine drugs and carcinogens, but predicted acetylator NAT2 phenotypes were not associated with insulin sensitivity. In a murine adipocyte cell line, silencing of NAT2 ortholog Nat1 decreased insulin-mediated glucose uptake, increased basal and isoproterenol-stimulated lipolysis, and decreased adipocyte differentiation, while Nat1 overexpression produced opposite effects. Nat1-deficient mice had elevations in fasting blood glucose, insulin, and triglycerides and decreased insulin sensitivity, as measured by glucose and insulin tolerance tests, with intermediate effects in Nat1 heterozygote mice. Our results support a role for NAT2 in insulin sensitivity.

Published
2016

4. Genome-Wide Association Study of the Modified Stumvoll Insulin Sensitivity Index Identifies BCL2 and FAM19A2 as Novel Insulin Sensitivity Loci

Author

Walford, Geoffrey A, Gustafsson, Stefan, Rybin, Denis, Stančáková, Alena, Chen, Han, Liu, Ching-Ti, Hong, Jaeyoung, Jensen, Richard A, Rice, Ken, Morris, Andrew P, Mägi, Reedik, Tönjes, Anke, Prokopenko, Inga, Kleber, Marcus E, Delgado, Graciela, Silbernagel, Günther, Jackson, Anne U, Appel, Emil V, Grarup, Niels, Lewis, Joshua P, Montasser, May E, Landenvall, Claes, Staiger, Harald, Luan, Jian'an, Frayling, Timothy M, Weedon, Michael N, Xie, Weijia, Morcillo, Sonsoles, Martínez-Larrad, María Teresa, Biggs, Mary L, Chen, Yii-Der Ida, Corbaton-Anchuelo, Arturo, Færch, Kristine, Gómez-Zumaquero, Juan Miguel, Goodarzi, Mark O, Kizer, Jorge R, Koistinen, Heikki A, Leong, Aaron, Lind, Lars, Lindgren, Cecilia, Machicao, Fausto, Manning, Alisa K, Martín-Núñez, Gracia María, Rojo-Martínez, Gemma, Rotter, Jerome I, Siscovick, David S, Zmuda, Joseph M, Zhang, Zhongyang, Serrano-Rios, Manuel, Smith, Ulf, Soriguer, Federico, Hansen, Torben, Jørgensen, Torben J, Linnenberg, Allan, Pedersen, Oluf, Walker, Mark, Langenberg, Claudia, Scott, Robert A, Wareham, Nicholas J, Fritsche, Andreas, Häring, Hans-Ulrich, Stefan, Norbert, Groop, Leif, O'Connell, Jeff R, Boehnke, Michael, Bergman, Richard N, Collins, Francis S, Mohlke, Karen L, Tuomilehto, Jaakko, März, Winfried, Kovacs, Peter, Stumvoll, Michael, Psaty, Bruce M, Kuusisto, Johanna, Laakso, Markku, Meigs, James B, Dupuis, Josée, Ingelsson, Erik, and Florez, Jose C

Subjects
Male, Prevention, Human Genome, Diabetes, Single Nucleotide, CC, Medical and Health Sciences, Endocrinology & Metabolism, Proto-Oncogene Proteins c-bcl-2, Insulin Receptor Substrate Proteins, Genetics, Humans, 2.1 Biological and endogenous factors, Genetic Predisposition to Disease, Female, Insulin Resistance, Chemokines, Polymorphism, Aetiology, Metabolic and endocrine, Genome-Wide Association Study
Abstract

Genome-wide association studies (GWAS) have found few common variants that influence fasting measures of insulin sensitivity. We hypothesized that a GWAS of an integrated assessment of fasting and dynamic measures of insulin sensitivity would detect novel common variants. We performed a GWAS of the modified Stumvoll Insulin Sensitivity Index (ISI) within the Meta-Analyses of Glucose and Insulin-Related Traits Consortium. Discovery for genetic association was performed in 16,753 individuals, and replication was attempted for the 23 most significant novel loci in 13,354 independent individuals. Association with ISI was tested in models adjusted for age, sex, and BMI and in a model analyzing the combined influence of the genotype effect adjusted for BMI and the interaction effect between the genotype and BMI on ISI (model 3). In model 3, three variants reached genome-wide significance: rs13422522 (NYAP2; P = 8.87 × 10(-11)), rs12454712 (BCL2; P = 2.7 × 10(-8)), and rs10506418 (FAM19A2; P = 1.9 × 10(-8)). The association at NYAP2 was eliminated by conditioning on the known IRS1 insulin sensitivity locus; the BCL2 and FAM19A2 associations were independent of known cardiometabolic loci. In conclusion, we identified two novel loci and replicated known variants associated with insulin sensitivity. Further studies are needed to clarify the causal variant and function at the BCL2 and FAM19A2 loci.

Published
2016

5. Identification and validation of N-acetyltransferase 2 as an insulin sensitivity gene

Author

Knowles, Joshua W, Xie, Weijia, Zhang, Zhongyang, Chennamsetty, Indumathi, Assimes, Themistocles L, Paananen, Jussi, Hansson, Ola, Pankow, James, Goodarzi, Mark O, Carcamo-Orive, Ivan, Morris, Andrew P, Chen, Yii-Der I, Mäkinen, Ville-Petteri, Ganna, Andrea, Mahajan, Anubha, Guo, Xiuqing, Abbasi, Fahim, Greenawalt, Danielle M, Lum, Pek, Molony, Cliona, Lind, Lars, Lindgren, Cecilia, Raffel, Leslie J, Tsao, Philip S, RISC (Relationship between Insulin Sensitivity and Cardiovascular Disease) Consortium, EUGENE2 (European Network on Functional Genomics of Type 2 Diabetes) Study, GUARDIAN (Genetics UndeRlying DIAbetes in HispaNics) Consortium, SAPPHIRe (Stanford Asian and Pacific Program for Hypertension and Insulin Resistance) Study, Schadt, Eric E, Rotter, Jerome I, Sinaiko, Alan, Reaven, Gerald, Yang, Xia, Hsiung, Chao A, Groop, Leif, Cordell, Heather J, Laakso, Markku, Hao, Ke, Ingelsson, Erik, Frayling, Timothy M, Weedon, Michael N, Walker, Mark, and Quertermous, Thomas

Subjects
Adult, Asian Continental Ancestry Group, Male, GUARDIAN (Genetics UndeRlying DIAbetes in HispaNics) Consortium, Glycated Hemoglobin A, EUGENE2 (European Network on Functional Genomics of Type 2 Diabetes) Study, Adolescent, Arylamine N-Acetyltransferase, Knockout, Lipolysis, European Continental Ancestry Group, Immunology, Taiwan, Glycosylated, Coronary Disease, Medical and Health Sciences, Mice, Young Adult, Gene Frequency, 3T3-L1 Cells, Animals, Humans, Point Mutation, Prospective Studies, Polymorphism, Child, Hypertriglyceridemia, Adipogenesis, SAPPHIRe (Stanford Asian and Pacific Program for Hypertension and Insulin Resistance) Study, Hemoglobin A, Single Nucleotide, Middle Aged, United States, Isoenzymes, Europe, Glucose, Hyperglycemia, Mutation, RISC (Relationship between Insulin Sensitivity and Cardiovascular Disease) Consortium, Female, Insulin Resistance, Missense, Hispanic Americans, Genome-Wide Association Study
Abstract

Decreased insulin sensitivity, also referred to as insulin resistance (IR), is a fundamental abnormality in patients with type 2 diabetes and a risk factor for cardiovascular disease. While IR predisposition is heritable, the genetic basis remains largely unknown. The GENEticS of Insulin Sensitivity consortium conducted a genome-wide association study (GWAS) for direct measures of insulin sensitivity, such as euglycemic clamp or insulin suppression test, in 2,764 European individuals, with replication in an additional 2,860 individuals. The presence of a nonsynonymous variant of N-acetyltransferase 2 (NAT2) [rs1208 (803A>G, K268R)] was strongly associated with decreased insulin sensitivity that was independent of BMI. The rs1208 "A" allele was nominally associated with IR-related traits, including increased fasting glucose, hemoglobin A1C, total and LDL cholesterol, triglycerides, and coronary artery disease. NAT2 acetylates arylamine and hydrazine drugs and carcinogens, but predicted acetylator NAT2 phenotypes were not associated with insulin sensitivity. In a murine adipocyte cell line, silencing of NAT2 ortholog Nat1 decreased insulin-mediated glucose uptake, increased basal and isoproterenol-stimulated lipolysis, and decreased adipocyte differentiation, while Nat1 overexpression produced opposite effects. Nat1-deficient mice had elevations in fasting blood glucose, insulin, and triglycerides and decreased insulin sensitivity, as measured by glucose and insulin tolerance tests, with intermediate effects in Nat1 heterozygote mice. Our results support a role for NAT2 in insulin sensitivity.

Published
2015

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