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Experimental Diabetes Research
Volume 2012 (2012), Article ID 789174, 12 pages
http://dx.doi.org/10.1155/2012/789174
Review Article

Insulin Resistance and Cancer Risk: An Overview of the Pathogenetic Mechanisms

1Department of Health Sciences, Magna Græcia University of Catanzaro, Viale Europa (Località Germaneto), 88100 Catanzaro, Italy
2Clinical Pathology, Magna Græcia University of Catanzaro, Viale Europa (Località Germaneto), 88100 Catanzaro, Italy
3Endocrinology, Magna Græcia University of Catanzaro, Viale Europa (Località Germaneto), 88100 Catanzaro, Italy

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.

Abstract

Insulin resistance 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 insulin-like growth factor 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 increased risk 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 summarize recent 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.