The association of PTEN/PI3K/Akt pathway gene expression with insulin indices in adipose tissues of non-diabetic female adults: a cross-sectional study

Insulin resistance (IR) is a complex metabolic condition that serves as a common thread connecting type 2 diabetes (T2DM), metabolic syndrome (MetS), cardiovascular disease (CVD), and even certain cancer outcomes. Understanding and addressing IR is crucial for the prevention and management of these interrelated health challenges. Adipose tissue (AT) is one of the main targets for insulin action, and insulin suppresses lipolysis in this tissue. This study aimed to investigate the relationship between genes in the PI3K/AKT pathway and the negative regulator of this pathway, PTEN, with indices of insulin resistance in human adipose tissue. In this cross-sectional study, 118 women, aged ≥ 18 years were selected among patients who were admitted to hospitals (Mostafa Khomeini and Khatam Al-Anbia, Tehran, Iran) for elective and minimal abdominal surgery including appendectomy and umbilical and inguinal hernia repair. Anthropometric and laboratory parameters, physical activity, and dietary intake were measured. Expression of PTEN, PI3K, and Akt genes were evaluated using Real-Time qRT-PCR. Insulin-related metabolic indices such as hyperinsulinemia, HOMA-IR, HOMA-B, HOMA-S, QUICKI, and TyG indexes were defined and calculated. After controlling age, physical activity, BMI, and energy intake, the expression of SAT PTEN was negatively associated with IR (β=-4.475, P = 0.021) and positively associated with HOMA-B cell dysfunction (β = 4.944, P = 0.012). VAT PI3K was positively associated with hyperinsulinemia (β = 8.802, P = 0.008) and IR (β = 7.710, P = 0.028). Higher VAT Akt gene expression was associated with higher hyperinsulinemia (β = 6.684, P = 0.003) and IR (β = 5.296, P = 0.027). Moreover, higher SAT Akt mRNA level was associated with FPI (β = 0.128, P = 0.048), and hyperinsulinemia (β = 4.201, P = 0.008). The findings of the present study suggest that hyperinsulinemia and insulin resistance (HOMA-IR), are directly associated with PI3K and Akt expression yet they show an inverse relationship with PTEN, which inhibits the insulin pathway.