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

Abstract 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...

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Main Authors: Maryam Zarkesh, Romina Saba, Hamidreza Aghazadeh, Farshad Teymoori, Mahdi Akbarzadeh, Golaleh Asghari, Marzieh Montazeri, Asghar Ghasemi, Emad Yuzbashian, Azita Zadeh-Vakili, Mehdi Hedayati, Alireza Khalaj
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Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-05233-4
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author Maryam Zarkesh
Romina Saba
Hamidreza Aghazadeh
Farshad Teymoori
Mahdi Akbarzadeh
Golaleh Asghari
Marzieh Montazeri
Asghar Ghasemi
Emad Yuzbashian
Azita Zadeh-Vakili
Mehdi Hedayati
Alireza Khalaj
author_facet Maryam Zarkesh
Romina Saba
Hamidreza Aghazadeh
Farshad Teymoori
Mahdi Akbarzadeh
Golaleh Asghari
Marzieh Montazeri
Asghar Ghasemi
Emad Yuzbashian
Azita Zadeh-Vakili
Mehdi Hedayati
Alireza Khalaj
author_sort Maryam Zarkesh
collection DOAJ
description Abstract 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.
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spelling doaj-art-e6b4ea6ce65c47eabfc2c046860ffad12025-08-20T03:37:23ZengNature PortfolioScientific Reports2045-23222025-07-0115111210.1038/s41598-025-05233-4The association of PTEN/PI3K/Akt pathway gene expression with insulin indices in adipose tissues of non-diabetic female adults: a cross-sectional studyMaryam Zarkesh0Romina Saba1Hamidreza Aghazadeh2Farshad Teymoori3Mahdi Akbarzadeh4Golaleh Asghari5Marzieh Montazeri6Asghar Ghasemi7Emad Yuzbashian8Azita Zadeh-Vakili9Mehdi Hedayati10Alireza Khalaj11Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Molecular Biology, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical SciencesCellular and Molecular Endocrine Research Center, Research Institute for Endocrine Molecular Biology, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical SciencesCellular and Molecular Endocrine Research Center, Research Institute for Endocrine Molecular Biology, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical SciencesNutritional Sciences Research Center, Iran University of Medical SciencesCellular and Molecular Endocrine Research Center, Research Institute for Endocrine Molecular Biology, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical SciencesDepartment of Clinical Nutrition and Dietetics, Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical SciencesEndocrine Research Center, Research Institute for Endocrine Disorders, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical SciencesEndocrine Physiology Research Center, Research Institute for Endocrine Molecular Biology, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical SciencesDepartment of Agricultural, Food and Nutritional Science, University of AlbertaEndocrine Research Center, Research Institute for Endocrine Disorders, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical SciencesCellular and Molecular Endocrine Research Center, Research Institute for Endocrine Molecular Biology, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical SciencesTehran Obesity Treatment Center, Department of Surgery, Shahed UniversityAbstract 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.https://doi.org/10.1038/s41598-025-05233-4Phosphatase and tensin homologuePhosphatidylinositol-3-kinaseAKT serine/Threonine kinaseInsulin resistanceAdipose tissuesFemales
spellingShingle Maryam Zarkesh
Romina Saba
Hamidreza Aghazadeh
Farshad Teymoori
Mahdi Akbarzadeh
Golaleh Asghari
Marzieh Montazeri
Asghar Ghasemi
Emad Yuzbashian
Azita Zadeh-Vakili
Mehdi Hedayati
Alireza Khalaj
The association of PTEN/PI3K/Akt pathway gene expression with insulin indices in adipose tissues of non-diabetic female adults: a cross-sectional study
Scientific Reports
Phosphatase and tensin homologue
Phosphatidylinositol-3-kinase
AKT serine/Threonine kinase
Insulin resistance
Adipose tissues
Females
title The association of PTEN/PI3K/Akt pathway gene expression with insulin indices in adipose tissues of non-diabetic female adults: a cross-sectional study
title_full The association of PTEN/PI3K/Akt pathway gene expression with insulin indices in adipose tissues of non-diabetic female adults: a cross-sectional study
title_fullStr The association of PTEN/PI3K/Akt pathway gene expression with insulin indices in adipose tissues of non-diabetic female adults: a cross-sectional study
title_full_unstemmed The association of PTEN/PI3K/Akt pathway gene expression with insulin indices in adipose tissues of non-diabetic female adults: a cross-sectional study
title_short The association of PTEN/PI3K/Akt pathway gene expression with insulin indices in adipose tissues of non-diabetic female adults: a cross-sectional study
title_sort association of pten pi3k akt pathway gene expression with insulin indices in adipose tissues of non diabetic female adults a cross sectional study
topic Phosphatase and tensin homologue
Phosphatidylinositol-3-kinase
AKT serine/Threonine kinase
Insulin resistance
Adipose tissues
Females
url https://doi.org/10.1038/s41598-025-05233-4
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