Insulin resistance and cancer risk: an overview of the pathogenetic mechanisms.
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.
Department of Health Sciences, Magna Græcia University of Catanzaro, Viale Europa (Località Germaneto), 88100 Catanzaro, Italy.
Biagio
B
Arcidiacono
Stefania
S
Iiritano
Aurora
A
Nocera
Katiuscia
K
Possidente
Maria T
MT
Nevolo
Valeria
V
Ventura
Daniela
D
Foti
Eusebio
E
Chiefari
Antonio
A
Brunetti
D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D004249:DNA Damage; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008954:Models, Biological; D009369:Neoplasms / Q000175:diagnosis / Q000473:pathology* / Q000503:physiopathology; D009765:Obesity / Q000503:physiopathology; D010053:Ovary / Q000378:metabolism; D017382:Reactive Oxygen Species; D012306:Risk; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013256:Steroids / Q000378:metabolism
D017382:Reactive Oxygen Species; D012738:Sex Hormone-Binding Globulin; D013256:Steroids; D007334:Insulin-Like Growth Factor I