Activation of the PI3K/Akt/mTOR/p70S6K1 Signaling Cascade in the Mononuclear Cells of Peripheral Blood: Association with Insulin and Insulin-Like Growth Factor Levels in the Blood of Patients with Cancer and Diabetes

Вацеба, Т.С.; Соколова, Л.К.; Pushkarev, V.V.; Kovzun, O.I.; Гуда, Б.Б.; Тronko, М.D.

doi:10.3103/s0095452719060112

Cited by 8 publications

(9 citation statements)

References 22 publications

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“…In hyperinsulinemia, insulin cross-reacts with IGF-1 receptors (IGF-1R) and, conversely, IGF-1 with insulin receptors (IR). The effect of insulin and IGF-1 is accomplished through the stimulation of the PI3K/Akt/mTOR and MAPK/mTOR signalling pathways, which are involved in metabolism control and in oncogenesis [13,18].…”

Section: Resultsmentioning

confidence: 99%

The impact of obesity on the development of certain cancers in patients with type 2 diabetes

et al. 2021

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The aim of the study was to investigate the effect of obesity on the development of cancer of certain localizations in patients with type 2 diabetes mellitus (T2D) and to explain the association mechanisms of obesity in diabetes and cancer. The study included retrospective analysis of first time diagnosed cancer cases in patients with T2D in 2012-2016 in Ivano-Frankivsk region. Analysis of the data was carried out using Statistica 12.0 (StatSoft Inc., USA) program. The data are presented in the tables as M ± SD (M ± standard deviation). Differences between the studied parameters were determined using the ANOVA- test, taking into account the Bonferroni correction. The relationship between the studied data was evaluated using the criterion of chi-square with Yates correction (χ²). The odds ratio (OR), 95% confidence interval, the positive and negative predictive value were calculated to determine the association between two events. The differences were considered significant at p < 0.05. According to the results, 533 cases of the first time diagnosed cancer were detected in patients with T2D. It was found that obesity is inherent in women with breast, uterine, ovarian and colorectal cancer; for men with prostate cancer and with colorectal cancer. According to the criterion of χ², the effect of obesity on the incidence of breast cancer in women (x2=8.46; p<0.05), and prostate cancer (x2=7.02; p<0.05) and colorectal cancer (x2=7.94; p<0.05) in men was proven. OR revealed an increased risk of breast cancer in women [OR=2.06; 95% CI (1.28-3.29); p<0.05], and prostate cancer [OR=2.94; 95% CI (1.37-6.32); p<0.05] and colorectal cancer [OR=2.87; 95% CI (1.42-5.82); p<0.05] in men associated with obesity. Thus, among patients with T2D, obesity increases the risk of breast cancer in women, prostate cancer and colorectal cancer in men. The mechanisms of association of obesity and cancer in patients with T2D are hyperglycemia, hyperinsulinemia, cytokine imbalance, hyperestrogenism (in estrogen-dependent cancer), and intestinal dysbiosis (in colorectal cancer).

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Section: Resultsmentioning

confidence: 99%

The impact of obesity on the development of certain cancers in patients with type 2 diabetes

et al. 2021

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“…Here, we detected AEBP1 mRNA in plasma-derived exosomal RNA and confirmed its upregulated pattern in DKD patients. According to previous studies, upregulated AEBP1 could be regulated by the transcription factor CREB and the PI3K/Akt pathway in melanoma cells [ 43 ], and activation of the PI3K/Akt signaling cascade could be found in diabetic patient-derived peripheral blood mononuclear cells (PBMCs) [ 44 ]. Therefore, these PBMCs could be the possible origin of the AEBP1-containing exosomes.…”

Section: Discussionmentioning

confidence: 99%

Extracellular vesicle-derived AEBP1 mRNA as a novel candidate biomarker for diabetic kidney disease

et al. 2021

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Background A novel and improved methodology is still required for the diagnosis of diabetic kidney disease (DKD). The aim of the present study was to identify novel biomarkers using extracellular vesicle (EV)-derived mRNA based on kidney tissue microarray data. Methods Candidate genes were identified by intersecting the differentially expressed genes (DEGs) and eGFR-correlated genes using the GEO datasets GSE30528 and GSE96804, followed by clinical parameter correlation and diagnostic efficacy assessment. Results Fifteen intersecting genes, including 8 positively correlated genes, B3GALT2, CDH10, MIR3916, NELL1, OCLM, PRKAR2B, TREM1 and USP46, and 7 negatively correlated genes, AEBP1, CDH6, HSD17B2, LUM, MS4A4A, PTN and RASSF9, were confirmed. The expression level assessment results revealed significantly increased levels of AEBP1 in DKD-derived EVs compared to those in T2DM and control EVs. Correlation analysis revealed that AEBP1 levels were positively correlated with Cr, 24-h urine protein and serum CYC and negatively correlated with eGFR and LDL, and good diagnostic efficacy for DKD was also found using AEBP1 levels to differentiate DKD patients from T2DM patients or controls. Conclusions Our results confirmed that the AEBP1 level from plasma EVs could differentiate DKD patients from T2DM patients and control subjects and was a good indication of the function of multiple critical clinical parameters. The AEBP1 level of EVs may serve as a novel and efficacious biomarker for DKD diagnosis.

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“…All patients signed informed consent for the use of biomaterials in further diagnostic and scientific studies. Immediately after sampling, the blood was diluted in 2-fold with PBS (pH 7.4), and PBMC were isolated as described previously [8]. The collected PBMC were washed with PBS by centrifugation at 200 g to remove platelets and frozen at -80 °C until use.…”

Section: Methodsmentioning

confidence: 99%

Активація Кінази, Що Регулюється Позаклітинними Сигналами-1/2 (Еrк1/2), У Мононуклеарах Крові Людини За Діабету Та Автоімунного Тиреоїдиту

Пушкарев¹,

Соколова²,

Ковзун³

et al. 2020

Endokr.

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До складу мононуклеарних клітин периферичної крові (PBМC) в основному входять моноцити і лімфоцити, які беруть участь у розвитку цукрового діабету (ЦД), та інших автоімунних захворювань. Ret/Ras/Raf/MEK/ERK є сигнальним каскадом, який контролює такі клітинні процеси, як проліферація, виживання, ангіогенез, ріст і рухливість клітин. Метою роботи було дослідження активації в PBМC головної ефекторної протеїнкінази цього каскаду — ERK1/2. Матеріал і методи. Матеріалом роботи була кров здорових осіб, пацієнтів із діабетом 2-го типу, з діабетом 2-го типу й автоімунним тиреоїдитом (АІТ), із діабетом 2-го типу та раком щитоподібної залози, із діабетом 1-го типу, із діабетом 1-го типу й АІТ. Для визначення кількості фосфо-ERK1/2 (ф-Thr202/Thr204 і Thr185/Tyr187 відповідно) використовували набори для імуноферментного аналізу 85-86012 («Invitrogen», СШA). Результати. Пацієнтів розподілили на 6 груп: 1 — контроль — здорові особи, репрезентативні за віком та ІМТ, 2 — пацієнти з діабетом 2-го типу,3 — пацієнти з діабетом 2-го типу й АІТ, 4 — пацієнти з діабетом 2-го типу та раком щитоподібної залози, 5 — пацієнти з діабетом 1-го типу,6 — пацієнти з діабетом 1-го типу і АІТ. Показано, що активації ЕRК1/2 у РВМС хворих на діабет 2-го типу та рак не спостерігалося, тоді як у хворих на діабет 1-го типу або з АІТ вона суттєво зростала. Натомість у хворих на діабет 1-го типу з АІТ активація ЕRК1/2 у РВМС знижувалася до контрольного рівня, що можна пояснити конкуренцією між двома автоімунними процесами за спільні сигнальні шляхи. Висновок. У пацієнтів з автоімунними захворюваннями (діабет 1-го типу або АІТ) у PBМC відбувається активація МАРК/ЕRК-каскаду.

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Activation of the PI3K/Akt/mTOR/p70S6K1 Signaling Cascade in the Mononuclear Cells of Peripheral Blood: Association with Insulin and Insulin-Like Growth Factor Levels in the Blood of Patients with Cancer and Diabetes

Cited by 8 publications

References 22 publications

The impact of obesity on the development of certain cancers in patients with type 2 diabetes

The impact of obesity on the development of certain cancers in patients with type 2 diabetes

Extracellular vesicle-derived AEBP1 mRNA as a novel candidate biomarker for diabetic kidney disease

Активація Кінази, Що Регулюється Позаклітинними Сигналами-1/2 (Еrк1/2), У Мононуклеарах Крові Людини За Діабету Та Автоімунного Тиреоїдиту

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