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Abstract
Numerous studies have demonstrated the impact of diabetes-associated factors on the development of malignant diseases in patients with type 2 diabetes mellitus (T2DM). Active research is underway to identify biochemical markers of oncogenesis for early cancer diagnosis and prevention. The activity of components of the PI3K/Akt/mTOR signaling pathway is being investigated as potential oncogenic markers in patients with T2DM. Purpose. To determine the activity of the terminal part of the PI3K/Akt/mTORC1/p70s6k signaling cascade in patients with T2DM and to assess the influence of metabolic factors on its activation. Material and methods. A total of 44 individuals were examined: group I — healthy controls
(n=16), group II — patients with T2DM (n=28). Anthropometric parameters (height, weight) and laboratory indicators were assessed: fasting blood glucose, glycated hemoglobin (HbA1c), insulin, insulin-like growth factor 1 (IGF-1), and the level of phosphorylated p70S6 kinase (phospho-p70s6k) in peripheral blood mononuclear cells. The body mass index (BMI) and HOMA-IR index were calculated mathematically. Correlation analyses were performed between the studied parameters. Results. Patients with T2DM had significantly higher levels of glycemia, HbA1c, insulin, IGF-1, and HOMA-IR compared to group I (p<0.05). A significantly increased level of phosphop70s6k was found in the peripheral blood mononuclear cells of patients with T2DM (p<0.05), indicating hyperactivation of the PI3K/Akt/mTOR pathway. In group II, a direct correlation was found between insulin levels and BMI (r=0.560; p<0.05), HOMA-IR (r=0.754; p<0.05), and IGF-1 levels (r=0.462; p<0.05). Additionally, phospho-p70s6k levels positively correlated with insulin (r=0.520; p<0.05) and HbA1c levels (r=0.370; p<0.05). Conclusions. Patients with T2DM exhibited increased levels of extracellular activators of insulin signaling, namely insulin and IGF-1. The elevated level of phosphorylated p70s6k (Thr389) supports the potential role of hyperactivation of the PI3K/Akt/mTOR pathway in oncogenesis in patients with T2DM. The observed direct correlation of phospho-p70s6k
(Thr389) with insulin and HbA1c levels in T2DM patients confirms the role of hyperinsulinemia and hyperglycemia in the activation of the PI3K/Akt/mTOR signaling pathway.
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