Insulin Resistance and Cancer: In Search for a Causal Link

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.

Association Between a Novel Metabolic Score for Insulin Resistance and Mortality in People With Diabetes

“…Sixthly, increasing scholars begin to pay attention to the role of metabolism in the occurrence and development of cancer, and we also tried to explore the relationship between IR and cancer-related mortality. Although previous studies have shown that IR and metabolic syndrome were associated with higher risks of cancer and cancer-related death ( 55 , 56 ), our study failed to find a linear or non-linear relationship between METS-IR and cancer-related mortality, which may be due to the heterogeneity of the study population and the small sample size. Finally, there may be other residual confounding factors that have not been controlled, such as oxidative stress, inflammatory, thrombotic status, and genetic susceptibility.…”

Obesity and Thyroid Cancer Risk: An Update

“…Obese individuals often have impaired insulin sensitivity, which causes pancreatic beta-cells to promote insulin production, leading to hyperinsulinemia and insulin resistance (IR) [88]. Several studies support the hypothesis of a link between IR and increased risk of many cancers, including TC [89][90][91][92]. Insulin is not only a metabolic hormone but also a cell growth factor that can stimulate the mitogenic cascade by activating the MAPK and mTOR pathways.…”

Association Between Dietary Fatty Acid Pattern and Risk of Oral Cancer

“…Inflammation was a key cause of the development and progression of many chronic diseases, including cancer ( 39 ). Moreover, inflammatory cytokines such as tumor necrosis factor (TNF)-a, induced by SFA, may influence insulin sensitivity ( 40 ), which favored the establishment of a pro-tumorigenic environment ( 41 ). Fatty acylation was another potential carcinogenic mechanism of SFA.…”