Assessing the Link between Diabetic Metabolic Dysregulation and Breast Cancer Progression

Abstract

Diabetes mellitus is a burdensome disease that affects various cellular functions through altered glucose metabolism. Several reports have linked diabetes to cancer development; however, the exact molecular mechanism of how diabetes-related traits contribute to cancer progression is not fully understood. The current study aimed to explore the molecular mechanism underlying the potential effect of hyperglycemia combined with hyperinsulinemia on the progression of breast cancer cells. To this end, gene dysregulation induced by the exposure of MCF7 breast cancer cells to hyperglycemia (HG), or a combination of hyperglycemia and hyperinsulinemia (HGI), was analyzed using a microarray gene expression assay. Hyperglycemia combined with hyperinsulinemia induced differential expression of 45 genes (greater than or equal to two-fold), which were not shared by other treatments. On the other hand, in silico analysis performed using a publicly available dataset (GEO: GSE150586) revealed differential upregulation of 15 genes in the breast tumor tissues of diabetic patients with breast cancer when compared with breast cancer patients with no diabetes. SLC26A11, ALDH1A3, MED20, PABPC4 and SCP2 were among the top upregulated genes in both microarray data and the in silico analysis. In conclusion, hyperglycemia combined with hyperinsulinemia caused a likely unique signature that contributes to acquiring more carcinogenic traits. Indeed, these findings might potentially add emphasis on how monitoring diabetes-related metabolic alteration as an adjunct to diabetes therapy is important in improving breast cancer outcomes. However, further detailed studies are required to decipher the role of the highlighted genes, in this study, in the pathogenesis of breast cancer in patients with a different glycemic index.

Ketosis Suppression and Ageing (KetoSAge): The Effects of Suppressing Ketosis in Long Term Keto-Adapted Non-Athletic Females

“…Considering that our cohort is female, it is imperative to recognise the links between hyperinsulinaemia, metabolic health, and breast cancer. Women with diabetes have been shown to exhibit poorer outcomes for breast cancer compared to their non-diabetic counterparts [66]. Consistent with these findings, in vitro research has shown that treating cancer cells, particularly breast and pancreatic, with high levels of glucose initiates molecular alterations such as phosphorylation of EGFR, which promotes their proliferation [125][126][127].…”

“…Considering that our cohort is exclusively female, it is imperative to recognise, for global population health, the pressing importance of focusing on diabetes, hyperinsulinaemia (insulin may be inside reference ranges; however, chronic hypoketonaemia may indicate an individual's hyperinsulinaemia threshold), obesity, and breast cancer. Given their widespread prevalence [65][66][67][68], understanding the intricate links between these conditions is critical in order to prevent occurrence and to improve outcomes. Our participant data show that long-term NK reduces fasting insulin, IGF-1, and glucose.…”