Resistencia A La Insulina Y Cancer

Hindawi Publishing Corporation Experimental Diabetes Research Volume 2012, Article ID 789174, 12 pages doi:10.1155/2012/789174

Review Article Insulin Resistance and Cancer Risk: An Overview of the Pathogenetic Mechanisms
Biagio Arcidiacono,1 Stefania Iiritano,1 Aurora Nocera,1 Katiuscia Possidente,1 Maria T. Nevolo,1 Valeria Ventura,1 Daniela Foti,1, 2 Eusebio Chiefari,1 and AntonioBrunetti1, 3
1 Department 2 Clinical

of Health Sciences, Magna Græcia University of Catanzaro, Viale Europa (Localit` Germaneto), 88100 Catanzaro, Italy a Pathology, Magna Græcia University of Catanzaro, Viale Europa (Localit` Germaneto), 88100 Catanzaro, Italy a 3 Endocrinology, Magna Græcia University of Catanzaro, Viale Europa (Localit` Germaneto), 88100 Catanzaro, Italy a Correspondence should beaddressed to Antonio Brunetti, brunetti@unicz.it Received 29 January 2012; Accepted 10 April 2012 Academic Editor: Chien-Jen Chen Copyright © 2012 Biagio Arcidiacono et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Insulinresistance is common in individuals with obesity or type 2 diabetes (T2D), in which circulating insulin levels are frequently increased. Recent epidemiological and clinical evidence points to a link between insulin resistance and cancer. The mechanisms for this association are unknown, but hyperinsulinaemia (a hallmark of insulin resistance) and the increase in bioavailable insulinlike growthfactor I (IGF-I) appear to have a role in tumor initiation and progression in insulin-resistant patients. Insulin and IGF-I inhibit the hepatic synthesis of sex-hormone binding globulin (SHBG), whereas both hormones stimulate the ovarian synthesis of sex steroids, whose effects, in breast epithelium and endometrium, can promote cellular proliferation and inhibit apoptosis. Furthermore, an increasedrisk of cancer among insulin-resistant patients can be due to overproduction of reactive oxygen species (ROS) that can damage DNA contributing to mutagenesis and carcinogenesis. On the other hand, it is possible that the abundance of inflammatory cells in adipose tissue of obese and diabetic patients may promote systemic inflammation which can result in a protumorigenic environment. Here, we summarizerecent progress on insulin resistance and cancer, focusing on various implicated mechanisms that have been described recently, and discuss how these mechanisms may contribute to cancer initiation and progression.

1. Introduction/General Overview
Insulin resistance is a pathological condition in which insulin action is impaired in peripheral target tissues including skeletal muscle, liver,and adipose tissue. Initially, in individuals destined to develop T2D, the pancreatic beta cells increase insulin production to overcome insulin resistance and maintain euglycemia. Frank T2D in insulin-resistant individuals develops when beta cells fail to compensate [1, 2]. Also, insulin resistance is a cardinal feature of the metabolic syndrome, a quartet of vascular risk factors which include,in addition to insulin resistance, central obesity, dyslipidemia, and systemic hypertension [3]. With the exception of rare, monogenic forms of insulin resistance, common insulin resistance is a very heterogeneous disorder for which

both genetic and environmental factors jointly determine susceptibility [4]. The environmental component reflects the unfavorable global shift toward a westernlifestyle of overeating and sedentary habits, with obesity as the outcome [2, 5]. The genetic factor is linked to quantitative and/or qualitative defects in the insulin receptor (INSR) signaling pathway which regulates growth and metabolic responses to insulin, in insulin target cells and tissues [6]. Patients with insulin resistance show an increased morbidity and mortality, largely attributable to...