Activation of the PI3K/AKT/MTOR/P70S6K1 signaling cascade in peripheral blood mononuclear cells in patients with type 2 diabetes
Modern research shows that patients with diabetes mellitus have an increased risk of cancer. PI3K/Akt/mTOR/p70S6K1 signaling pathway plays an important role in the pathogenesis of cancer and diabetes. The aim of this study was to determine the state of РІ3K/Akt/mTORC1/p70S6K signaling cascade activi...
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| Format: | Article |
| Language: | English |
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National Academy of Sciences of Ukraine, Palladin Institute of Biochemistry
2020-12-01
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| Series: | The Ukrainian Biochemical Journal |
| Subjects: | |
| Online Access: | http://ukrbiochemjournal.org/wp-content/uploads/2020/12/Vatseba_6_20.pdf |
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| author | L. K. Sokolova V. M. Pushkarev O. I. Kovzun B. B. Guda V. V. Pushkarev M. D. Tronko N. V. Skrypnyk L. M. Zaiats |
| author_facet | L. K. Sokolova V. M. Pushkarev O. I. Kovzun B. B. Guda V. V. Pushkarev M. D. Tronko N. V. Skrypnyk L. M. Zaiats |
| author_sort | L. K. Sokolova |
| collection | DOAJ |
| description | Modern research shows that patients with diabetes mellitus have an increased risk of cancer. PI3K/Akt/mTOR/p70S6K1 signaling pathway plays an important role in the pathogenesis of cancer and diabetes. The aim of this study was to determine the state of РІ3K/Akt/mTORC1/p70S6K signaling cascade activity in peripheral mononuclear blood cells (PBMC) of patients with type 2 diabetes (T2D) relatively to the insulin and insulin-like growth factor (IGF-1) concentrations in blood plasma. Enzyme-linked immunosorbent assay was used to examine the levels of insulin and IGF-1 in blood plasma as well as the content of phosphorylated forms of Akt (Ser473), PRAS40 (Thr246), and p70S6K (Thr389) in PMBC. It was shown that in the blood plasma of patients with T2D the levels of insulin and IGF-1 were increased. Phosphorylation and activation of Akt by the mTORC2 protein kinase complex was not observed. At the same time, the relative degree of phosphorylation of mTORC1 inhibitor, PRAS40, and its substrate, p70S6K, was higher in PMBC of T2D patients in comparison with control values. These data suggest that phosphoinositide-dependent protein kinase 1 (PDK1) and, possibly, mitogen-activated protein kinase (MAPK) could mediate the effects of IGF-1 on Akt activation under type 2 diabetes. |
| first_indexed | 2024-03-09T08:44:52Z |
| format | Article |
| id | doaj.art-626b9fc2cdbf482fab87fe5de795d93a |
| institution | Directory Open Access Journal |
| issn | 2409-4943 2413-5003 |
| language | English |
| last_indexed | 2024-03-09T08:44:52Z |
| publishDate | 2020-12-01 |
| publisher | National Academy of Sciences of Ukraine, Palladin Institute of Biochemistry |
| record_format | Article |
| series | The Ukrainian Biochemical Journal |
| spelling | doaj.art-626b9fc2cdbf482fab87fe5de795d93a2023-12-02T15:44:20ZengNational Academy of Sciences of Ukraine, Palladin Institute of BiochemistryThe Ukrainian Biochemical Journal2409-49432413-50032020-12-0192611311810.15407/ubj92.06.113Activation of the PI3K/AKT/MTOR/P70S6K1 signaling cascade in peripheral blood mononuclear cells in patients with type 2 diabetesL. K. Sokolova0V. M. Pushkarev1O. I. Kovzun2B. B. Guda3V. V. Pushkarev4M. D. Tronko5https://orcid.org/0000-0001-7421-0981N. V. Skrypnyk6L. M. Zaiats7SI “V.P. Komisarenko Institute of Endocrinology and Metabolism of NAMS of Ukraine”, Kyiv, UkraineSI “V.P. Komisarenko Institute of Endocrinology and Metabolism of NAMS of Ukraine”, Kyiv, UkraineSI “V.P. Komisarenko Institute of Endocrinology and Metabolism of NAMS of Ukraine”, Kyiv, UkraineSI “V.P. Komisarenko Institute of Endocrinology and Metabolism of NAMS of Ukraine”, Kyiv, UkraineSI “V.P. Komisarenko Institute of Endocrinology and Metabolism of NAMS of Ukraine”, Kyiv, UkraineSI “V.P. Komisarenko Institute of Endocrinology and Metabolism of NAMS of Ukraine”, Kyiv, UkraineIvano-Frankivsk National Medical University, Ivano-Frankivsk, UkraineIvano-Frankivsk National Medical University, Ivano-Frankivsk, UkraineModern research shows that patients with diabetes mellitus have an increased risk of cancer. PI3K/Akt/mTOR/p70S6K1 signaling pathway plays an important role in the pathogenesis of cancer and diabetes. The aim of this study was to determine the state of РІ3K/Akt/mTORC1/p70S6K signaling cascade activity in peripheral mononuclear blood cells (PBMC) of patients with type 2 diabetes (T2D) relatively to the insulin and insulin-like growth factor (IGF-1) concentrations in blood plasma. Enzyme-linked immunosorbent assay was used to examine the levels of insulin and IGF-1 in blood plasma as well as the content of phosphorylated forms of Akt (Ser473), PRAS40 (Thr246), and p70S6K (Thr389) in PMBC. It was shown that in the blood plasma of patients with T2D the levels of insulin and IGF-1 were increased. Phosphorylation and activation of Akt by the mTORC2 protein kinase complex was not observed. At the same time, the relative degree of phosphorylation of mTORC1 inhibitor, PRAS40, and its substrate, p70S6K, was higher in PMBC of T2D patients in comparison with control values. These data suggest that phosphoinositide-dependent protein kinase 1 (PDK1) and, possibly, mitogen-activated protein kinase (MAPK) could mediate the effects of IGF-1 on Akt activation under type 2 diabetes.http://ukrbiochemjournal.org/wp-content/uploads/2020/12/Vatseba_6_20.pdfperipheral blood mononuclear cellsaktpras40p70s6kinsulininsulin-like growth factortype 2 diabetes |
| spellingShingle | L. K. Sokolova V. M. Pushkarev O. I. Kovzun B. B. Guda V. V. Pushkarev M. D. Tronko N. V. Skrypnyk L. M. Zaiats Activation of the PI3K/AKT/MTOR/P70S6K1 signaling cascade in peripheral blood mononuclear cells in patients with type 2 diabetes The Ukrainian Biochemical Journal peripheral blood mononuclear cells akt pras40 p70s6k insulin insulin-like growth factor type 2 diabetes |
| title | Activation of the PI3K/AKT/MTOR/P70S6K1 signaling cascade in peripheral blood mononuclear cells in patients with type 2 diabetes |
| title_full | Activation of the PI3K/AKT/MTOR/P70S6K1 signaling cascade in peripheral blood mononuclear cells in patients with type 2 diabetes |
| title_fullStr | Activation of the PI3K/AKT/MTOR/P70S6K1 signaling cascade in peripheral blood mononuclear cells in patients with type 2 diabetes |
| title_full_unstemmed | Activation of the PI3K/AKT/MTOR/P70S6K1 signaling cascade in peripheral blood mononuclear cells in patients with type 2 diabetes |
| title_short | Activation of the PI3K/AKT/MTOR/P70S6K1 signaling cascade in peripheral blood mononuclear cells in patients with type 2 diabetes |
| title_sort | activation of the pi3k akt mtor p70s6k1 signaling cascade in peripheral blood mononuclear cells in patients with type 2 diabetes |
| topic | peripheral blood mononuclear cells akt pras40 p70s6k insulin insulin-like growth factor type 2 diabetes |
| url | http://ukrbiochemjournal.org/wp-content/uploads/2020/12/Vatseba_6_20.pdf |
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