Role of ENPP1 in insulin resistance without obesity

ENPP1 在不肥胖的胰岛素抵抗中的作用

基本信息

批准号：
7828113
负责人：
Nicola Abate
金额：
$ 27.82万
依托单位：
UNIVERSITY OF TEXAS MED BR GALVESTON
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-08-01 至 2012-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7828113
关键词：
Abate Abdomen Acute Adipocytes Adipose tissue Affect African American Animal Model Asians Biopsy Body fat Cardiovascular Diseases Cell membrane Cells Clinical Clinical Research Conflict (Psychology)Data Diabetes Mellitus Diet Epidemic Esterified Fatty Acids Ethnic Origin Evaluation Exons Exposure to Fat emulsion Fatty Acids Fatty acid glycerol esters Frequencies Gene Expression Gene Proteins Genes Genetic Polymorphism Genotype Glucose Glucose tolerance test Glutamine Glycerol Glycine Glycoproteins Heparin Hispanics Human In Vitro Individual Infusion procedures Insulin Insulin Receptor Insulin Resistance Insulin Resistance Pathway Intravenous Investigation Link Literature Measures Mediating Membrane Glycoproteins Metabolic Metabolic syndrome Metabolism Minority Groups Morbidity - disease rate Mus Muscle Nomads Non obese Non-Insulin-Dependent Diabetes Mellitus Nonesterified Fatty Acids Nucleotide pyrophosphatase Obesity Pathogenesis Pathway interactions Patients Peripheral Peritoneal Persons Physiology Plasma Population Positioning Attribute Predisposition Principal Investigator Proteins Race Receptor Protein-Tyrosine Kinases Receptor Signaling Reporting Research Personnel Risk Role Signal Transduction Skeletal Muscle South Asian Testing Tissues Transgenic Mice Variant Wild Type Mouse base cell type ethnic minority population fatty acid metabolism gain of function glucose disposal glucose metabolism insulin sensitivity insulin signaling intervention program mRNA Expression non-diabetic novel phosphoric diester hydrolase prevent programs protein expression receptor function response skeletal subcutaneous volunteer

项目摘要

DESCRIPTION (provided by applicant): The objective of this study is to evaluate the role of ENPP1 (also known as PC-1) in the pathogenesis of insulin resistance in non-obese persons. The effects of obesity on insulin resistance are of importance in the growing epidemic of the metabolic syndrome, type 2 diabetes and cardiovascular disease in the US population. However, it is recognized that groups of persons, often part of ethnic minorities of the US population, have excessive insulin resistance and risk for its associated metabolic complications, even without significant obesity. These individuals are more likely not to be captured in intervention programs to prevent diabetes and cardiovascular disease. Although the role of ENPP1 in the pathogenesis of insulin resistance and prediction of type 2 diabetes is still controversial, both data available from the literature and preliminary data by the principal investigator support the possibility that it could be a determinant of insulin resistance even in absence of obesity. ENPP1 is a glycoprotein that is located in the plasma membrane of most cell types and interacts with the insulin receptor so to determine a reduction in insulin signaling when it is over-expressed. A common polymorphism, the K121Q, associates with a "gain of function" so that higher susceptibility to insulin resistance appears to be present in the 121Q carriers. The overall hypothesis of this study is that ENPP1 over-expression and K121Q polymorphism act synergistically in determining adipose tissue insulin resistance and defective systemic insulin-mediated glucose utilization, even in absence of obesity. To test this hypothesis we propose to take the approach of evaluating ENPP1 K121Q polymorphism and gene/protein expression in adipose tissue and skeletal muscle of non-diabetic and non-obese persons who will be carefully studied for adipose tissue insulin resistance and insulin sensitivity to peripheral glucose disposal.

描述（由申请人提供）：本研究的目的是评估ENPP1（也称为PC-1）在非肥胖者胰岛素抵抗发病机理中的作用。肥胖对胰岛素抵抗的影响在美国人群中代谢综合征，2型糖尿病和心血管疾病的流行病中至关重要。但是，人们认识到，即使没有明显的肥胖症，也经常是美国人口中少数族裔的一群人，对其相关代谢并发症具有过多的胰岛素抵抗和风险。这些人更有可能在预防糖尿病和心血管疾病的干预计划中被捕。尽管ENPP1在胰岛素抵抗的发病机理中的作用和2型糖尿病的预测仍然是有争议的，但主要研究者的文献和初步数据可获得的数据，即使在肥胖症的情况下，也可能是胰岛素抵抗的可能性。 ENPP1是一种位于大多数细胞类型的质膜中的糖蛋白，并与胰岛素受体相互作用，因此确定胰岛素信号过表达时的降低。 K121Q是一种常见的多态性，它与“功能的增益”相关，因此在121Q载体中似乎存在更高的胰岛素抵抗易感性。这项研究的总体假设是，即使在没有肥胖症的情况下，ENPP1过表达和K121Q多态性在确定脂肪组织胰岛素抵抗和有缺陷的全身性胰岛素介导的葡萄糖利用方面具有协同作用。为了检验这一假设，我们建议采取评估脂肪组织中的ENPP1 K121Q多态性和基因/蛋白质表达的方法，这些方法将仔细研究非糖尿病和非肥胖者的非糖尿病和非肥胖者的骨骼肌肉，以确保脂肪组织的抗胰岛素耐药性和胰岛素抗胰岛素敏感性对外周的葡萄糖粘液糖性敏感性。

项目成果

期刊论文数量（11）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Role of ENPP1 on adipocyte maturation.

DOI：
10.1371/journal.pone.0000882
发表时间：
2007-09-12
期刊：
PloS one
影响因子：
3.7
作者：
Liang J;Fu M;Ciociola E;Chandalia M;Abate N
通讯作者：
Abate N

New Insights into the Role of ENPP1 in Insulin Resistance.

关于 ENPP1 在胰岛素抵抗中的作用的新见解。

DOI：
10.4172/2325-9736.1000e103
发表时间：
2012
期刊：
Journal of metabonomics & metabolites
影响因子：
0
作者：
Pan,Wentong;Chandalia,Manisha;Abate,Nicola
通讯作者：
Abate,Nicola

Peripheral adipose tissue insulin resistance alters lipid composition and function of hippocampal synapses.

DOI：
10.1111/jnc.13043
发表时间：
2015-04
期刊：
Journal of neurochemistry
影响因子：
4.7
作者：
Sallam HS;Tumurbaatar B;Zhang WR;Tuvdendorj D;Chandalia M;Tempia F;Laezza F;Taglialatela G;Abate N
通讯作者：
Abate N

Insulin resistance and body fat distribution in South Asian men compared to Caucasian men.

DOI：
10.1371/journal.pone.0000812
发表时间：
2007-08-29
期刊：
PLOS ONE
影响因子：
3.7
作者：
Chandalia, Manisha;Lin, Ping;Seenivasan, Thanalakshmi;Livingston, Edward H.;Snell, Peter G.;Grundy, Scott M.;Abate, Nicola
通讯作者：
Abate, Nicola

ENPP1/PC-1 K121Q and other predictors of posttransplant diabetes.

ENPP1/PC-1 K121Q 和移植后糖尿病的其他预测因子。

DOI：
10.1089/met.2010.0041
发表时间：
2011
期刊：
Metabolic syndrome and related disorders
影响因子：
2.1
作者：
Szuszkiewicz,Magdalene;Bell,Jason;Vazquez,Miguel;Adams-Huet,Beverley;Grundy,ScottM;Chandalia,Manisha;Abate,Nicola
通讯作者：
Abate,Nicola