The Role of Membrane Glycoprotein Plasma Cell Antigen 1/Ectonucleotide Pyrophosphatase Phosphodiesterase 1 in the Pathogenesis of Insulin Resistance and Related Abnormalities

@article{citeulike:2358232, abstract = {Insulin resistance is a major feature of most patients with type 2 diabetes mellitus (T2D). A number of laboratories have observed that membrane glycoprotein plasma cell antigen 1 (PC-1) [ectonucleotide pyrophosphatase phosphodiesterase 1] is either overexpressed or overactive in muscle, adipose tissue, fibroblasts, and other tissues of insulin-resistant individuals, both nondiabetic and diabetic. Moreover, in cultured cells in vitro and in transgenic mice in vivo, PC-1 overexpression impairs insulin stimulation of insulin receptor (IR) activation and downstream signaling. PC-1 binds to the connecting domain of the IR {alpha}-subunit that is located in residues 485599. The connecting domain transmits insulin binding in the {alpha}-subunit to activation of tyrosine kinase activation in the -subunit. When PC-1 is overexpressed, it inhibits insulin-induced IR -subunit tyrosine kinase activity. In addition, a polymorphism of PC-1 (K121Q) in various ethnic populations is closely associated with insulin resistance, T2D, and cardio- and nephrovascular diseases. The product of this polymorphism has a 2- to 3-fold increased binding affinity for the IR and is more potent than the wild-type PC-1 protein (K121K) in inhibiting the IR. These data suggest therefore that PC-1 is a candidate protein that may play a role in human insulin resistance and T2D by its overexpression, its overactivity, or both. 10.1210/er.2007-0004}, author = {Goldfine, Ira D. and Maddux, Betty A. and Youngren, Jack F. and Reaven, Gerald and Accili, Domenico and Trischitta, Vincenzo and Vigneri, Riccardo and Frittitta, Lucia }, citeulike-article-id = {2358232}, doi = {10.1210/er.2007-0004}, journal = {Endocr Rev}, keywords = {insulinresistance, molecular}, month = {February}, number = {1}, pages = {62--75}, posted-at = {2008-02-09 17:39:01}, priority = {2}, title = {The Role of Membrane Glycoprotein Plasma Cell Antigen 1/Ectonucleotide Pyrophosphatase Phosphodiesterase 1 in the Pathogenesis of Insulin Resistance and Related Abnormalities}, url = {http://dx.doi.org/10.1210/er.2007-0004}, volume = {29}, year = {2008} }

TY - JOUR ID - citeulike:2358232 L3 - citeulike-article-id:2358232 TI - The Role of Membrane Glycoprotein Plasma Cell Antigen 1/Ectonucleotide Pyrophosphatase Phosphodiesterase 1 in the Pathogenesis of Insulin Resistance and Related Abnormalities JF - Endocr Rev VL - 29 IS - 1 SP - 62 EP - 75 N2 - Insulin resistance is a major feature of most patients with type 2 diabetes mellitus (T2D). A number of laboratories have observed that membrane glycoprotein plasma cell antigen 1 (PC-1) [ectonucleotide pyrophosphatase phosphodiesterase 1] is either overexpressed or overactive in muscle, adipose tissue, fibroblasts, and other tissues of insulin-resistant individuals, both nondiabetic and diabetic. Moreover, in cultured cells in vitro and in transgenic mice in vivo, PC-1 overexpression impairs insulin stimulation of insulin receptor (IR) activation and downstream signaling. PC-1 binds to the connecting domain of the IR {alpha}-subunit that is located in residues 485599. The connecting domain transmits insulin binding in the {alpha}-subunit to activation of tyrosine kinase activation in the -subunit. When PC-1 is overexpressed, it inhibits insulin-induced IR -subunit tyrosine kinase activity. In addition, a polymorphism of PC-1 (K121Q) in various ethnic populations is closely associated with insulin resistance, T2D, and cardio- and nephrovascular diseases. The product of this polymorphism has a 2- to 3-fold increased binding affinity for the IR and is more potent than the wild-type PC-1 protein (K121K) in inhibiting the IR. These data suggest therefore that PC-1 is a candidate protein that may play a role in human insulin resistance and T2D by its overexpression, its overactivity, or both. 10.1210/er.2007-0004 KW - insulinresistance KW - molecular AU - Goldfine, Ira AU - Maddux, Betty AU - Youngren, Jack AU - Reaven, Gerald AU - Accili, Domenico AU - Trischitta, Vincenzo AU - Vigneri, Riccardo AU - Frittitta, Lucia PY - 2008/02/01/ UR - http://dx.doi.org/10.1210/er.2007-0004 ER -