Abstract
Insulin resistance (IR) is a condition which refers to individuals whose cells and tissues become insensitive to the peptide hormone, insulin. Over the recent years, a wealth of data has made it clear that a synergistic relationship exists between IR, type 2 diabetes mellitus, and cancer. Although the underlying mechanism(s) for this association remain unclear, it is well established that hyperinsulinemia, a hallmark of IR, may play a role in tumorigenesis. On the other hand, IR is strongly associated with visceral adiposity dysfunction and systemic inflammation, two conditions which favor the establishment of a pro-tumorigenic environment. Similarly, epigenetic modifications, such as DNA methylation, histone modifications, and non-coding RNA, in IR states, have been often associated with tumorigenesis in numerous types of human cancer. In addition to these observations, it is also broadly accepted that gut microbiota may play an intriguing role in the development of IR-related diseases, including type 2 diabetes and cancer, whereas potential chemopreventive properties have been attributed to some of the most commonly used antidiabetic medications. Herein we provide a concise overview of the most recent literature in this field and discuss how different but interrelated molecular pathways may impact on tumor development.
Highlights
The reduced response of peripheral target tissues to insulin action leads to insulin resistance (IR), a condition that is characterized by a compensatory increase of circulating insulin levels to maintain euglycemia
Overweight/obese men with IR appear to be at higher risk of getting prostate cancer, whereas an inverse correlation has been observed in patients with type 2 diabetes, suggesting that different mechanisms might link IR to prostate cancer development in these individuals [7]
A variety of genetic alterations leading to defects in insulin receptor (INSR) and/or other components of the insulin signaling pathway have been recognized as significant causes of uncommon forms of IR and diabetes [9]
Summary
The reduced response of peripheral target tissues to insulin action leads to insulin resistance (IR), a condition that is characterized by a compensatory increase of circulating insulin levels to maintain euglycemia. When the compensatory increase of insulin production can no longer compensate for IR, blood sugar rises and the insidious process leading to type 2 diabetes mellitus begins [1,2]. In this context, the liver, the major site of insulin clearance, plays a crucial role in ensuring euglycemia and insulin sensitivity [3,4]. A divergence in time trends in the incidence of cancer and other IR-related diseases has been observed: in contrast to that of obesity and type 2 diabetes, the incidence rate of cancer (all sites), which had been steadily increasing since the early 1970s, has currently plateaued [8]. We summarize the current status of knowledge on the connections between IR, obesity, type 2 diabetes, and cancer development, as well as the contribution of a series of molecules and pathways in both metabolic dysfunction and cancer risk
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