The Role of Insulin, IGF-1 and PRAS40 in the Processes of Oncogenesis in Women with Type 2 Diabetes Mellitus and Endometrial Cancer

Abstract

The objective of the research was to investigate the content of insulin, insulin-like growth factor-1 and phosphorylated protein kinase proline-rich Akt substrate of 40kDa and to determine their role in the activation of oncogenesis processes in women with type 2 diabetes mellitus and endometrial cancer.
 Materials and methods. There were examined 46 women who were divided into 4 groups: Group I included healthy women; Group II comprised women with type 2 diabetes mellitus; Group III included women with endometrial cancer; Group IV comprised women with endometrial cancer and co-existent type 2 diabetes mellitus. The levels of insulin, insulin-like growth factor-1, phospho- proline-rich Akt substrate of 40kDa were determined by immune-enzyme analysis. The compensation of diabetes mellitus was evaluated by hemoglobin A1c level using method of ion-exchange chromatography. The results obtained were analyzed using statistical analysis.
 Results. Women of all study groups had increased levels of insulin and insulin-like growth factor-1 as compared to the control group (p<0.05). The level of phospho-proline-rich Akt substrate of 40kDa increased in the patients of Group II (p<0.05) and the patients of Group III (p<0.05) and decreased in the patients of Group IV (p<0.05). According to correlation analysis, phospho-proline-rich Akt substrate of 40kDa was found to correlate with body mass index, insulin and insulin-like growth factor-1 in Group II, body mass index and insulin-like growth factor-1 in Group III and body mass index in Group IV (p<0.05).
 Conclusions. There was found an association between type 2 diabetes mellitus and endometrial cancer through obesity, hyperinsulinemia and insulin-like growth factor-1. The increase in phospho- proline-rich Akt substrate of 40kDa level was a sign of activation of mTOR and oncogenesis processes in the patients with type 2 diabetes mellitus. The decrease in phospho-proline-rich Akt substrate of 40kDa in the patients with endometrial cancer and co-existent type 2 diabetes mellitus can be explained by the influence of other intracellular regulatory systems or the effects of antidiabetic drugs, that requires additional study.