Multidrug resistance‐associated protein 4 (Mrp4) is a novel genetic factor in the pathogenesis of obesity and diabetes

Abstract

Obesity and diabetes have reached epidemic proportions globally. In the United States alone, almost 35% of the adult population are overweight and 12.2% are diabetic. 1,2 Both obesity and diabetes are considered major risk factors for cardiovascular disease (CVD). 3,4 Specifically, abdominal obesity is known to increase the risk of CVD through increased insulin resistance and inflammatory abnormalities. 3,5 An increase in adiposity (increase in adipose tissue

The Prostaglandin E2 Pathway and Breast Cancer Stem Cells: Evidence of Increased Signaling and Potential Targeting

“…After the rate-limiting steps of the COX enzymes, the multiple prostaglandin synthase isoforms PTGIS, TXA2S, PTGES, PTGDS, and PTGFS generate the different prostanoids: prostaglandin I2 (PGI 2 , also called prostacyclin), thromboxane A2 (TXA 2 ), prostaglandin E2 (PGE 2 ), prostaglandin D2 (PGD 2 ), and prostaglandin F2 alpha (PGF 2α ), respectively from PGH 2 ( Figure 1A ). The prostanoids are secreted by the multidrug resistance protein 4 (MRP4/ABCC4) and exert effects by binding to and activating specific G-protein coupled receptors expressed on target cells ( Figure 1A ) ( 25 ). Secreted PGE 2 acts in paracrine or autocrine fashion by binding prostaglandin E2 receptors 1, 2, 3 and 4 (EP1-4), which are respectively encoded by the PTGER1, PTGER2, PTGER3 , and PTGER4 genes ( Figure 1A ) ( 26 , 27 ).…”