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.
| Sallam, Hanaa S; Tumurbaatar, Batbayar; Zhang, Wen-Ru et al. (2015) Peripheral adipose tissue insulin resistance alters lipid composition and function of hippocampal synapses. J Neurochem 133:125-33 |
| Vargas, Gracie; Chandalia, Manisha; Jiang, Yongquan et al. (2013) Heterogeneity in subcutaneous adipose tissue morphology and metabolic complications in overweight and obese women. Metab Syndr Relat Disord 11:276-82 |
| Tuvdendorj, Demidmaa; Chandalia, Manisha; Batbayar, Tumurbaatar et al. (2013) Altered subcutaneous abdominal adipose tissue lipid synthesis in obese, insulin-resistant humans. Am J Physiol Endocrinol Metab 305:E999-E1006 |
| Zhang, Jifeng; Zhang, Yuan; Sun, Tingwan et al. (2013) Dietary obesity-induced Egr-1 in adipocytes facilitates energy storage via suppression of FOXC2. Sci Rep 3:1476 |
| Munoz, Alejandro; Abate, Nicola; Chandalia, Manisha (2013) Adipose tissue collagen and inflammation in nonobese Asian Indian men. J Clin Endocrinol Metab 98:E1360-3 |
| Chandalia, Manisha; Davila, Himara; Pan, Wentong et al. (2012) Adipose tissue dysfunction in humans: a potential role for the transmembrane protein ENPP1. J Clin Endocrinol Metab 97:4663-72 |
| Szuszkiewicz-Garcia, Magdalene; Li, Rong; Grundy, Scott M et al. (2012) Fat distribution and insulin resistance in young adult nonobese Asian Indian women. Metab Syndr Relat Disord 10:326-30 |
| Abate, Nicola (2012) Adipocyte maturation arrest: a determinant of systemic insulin resistance to glucose disposal. J Clin Endocrinol Metab 97:760-3 |
| Pan, Wentong; Chandalia, Manisha; Abate, Nicola (2012) New Insights into the Role of ENPP1 in Insulin Resistance. J Metabonomics Metab 1: |
| Pan, Wentong; Ciociola, Ester; Saraf, Manish et al. (2011) Metabolic consequences of ENPP1 overexpression in adipose tissue. Am J Physiol Endocrinol Metab 301:E901-11 |
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