Details

Autor(en) / Beteiligte

• Goldfine, Ira D
• Maddux, Betty A
• Youngren, Jack F
• Reaven, Gerald
• Accili, Domenico
• Trischitta, Vincenzo
• Vigneri, Riccardo
• Frittitta, Lucia

Titel

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

Ist Teil von

• Endocrine reviews, 2008-02, Vol.29 (1), p.62-75

Ort / Verlag

Bethesda, MD: Endocrine Society

Erscheinungsjahr

2008

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• 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 α-subunit that is located in residues 485–599. The connecting domain transmits insulin binding in the α-subunit to activation of tyrosine kinase activation in the β-subunit. When PC-1 is overexpressed, it inhibits insulin-induced IR β-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.