Long-Chain Acylcarnitines Decrease the Phosphorylation of the Insulin Receptor at Tyr1151 Through a PTP1B-Dependent Mechanism
| العنوان: | Long-Chain Acylcarnitines Decrease the Phosphorylation of the Insulin Receptor at Tyr1151 Through a PTP1B-Dependent Mechanism |
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| المؤلفون: | Karlis Vilks, Melita Videja, Eduards Sevostjanovs, Edgars Liepinsh, Aiga Grandane, Martins Katkevics, Maija Dambrova, Marina Makrecka-Kuka |
| المصدر: | International Journal of Molecular Sciences, Vol 22, Iss 6470, p 6470 (2021) International Journal of Molecular Sciences Volume 22 Issue 12 |
| بيانات النشر: | MDPI AG, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, medicine.medical_treatment, palmitoylcarnitine, chemistry.chemical_compound, insulin resistance, Insulin, Protein Phosphatase 2, Phosphorylation, insulin receptor, Biology (General), Spectroscopy, Protein Tyrosine Phosphatase, Non-Receptor Type 1, biology, General Medicine, Computer Science Applications, Cell biology, Chemistry, hormones, hormone substitutes, and hormone antagonists, QH301-705.5, long-chain acylcarnitines, CHO Cells, Models, Biological, Article, Catalysis, Inorganic Chemistry, Dephosphorylation, 03 medical and health sciences, Cricetulus, Carnitine, medicine, Animals, Physical and Theoretical Chemistry, QD1-999, Molecular Biology, Protein kinase B, Palmitoylcarnitine, Protein kinase C, 030102 biochemistry & molecular biology, Akt, Organic Chemistry, Protein phosphatase 2, Cyclic AMP-Dependent Protein Kinases, Receptor, Insulin, Insulin receptor, 030104 developmental biology, chemistry, biology.protein, Tyrosine, protein tyrosine phosphatase 1B, Proto-Oncogene Proteins c-akt |
| الوصف: | The accumulation of lipid intermediates may interfere with energy metabolism pathways and regulate cellular energy supplies. As increased levels of long-chain acylcarnitines have been linked to insulin resistance, we investigated the effects of long-chain acylcarnitines on key components of the insulin signalling pathway. We discovered that palmitoylcarnitine induces dephosphorylation of the insulin receptor (InsR) through increased activity of protein tyrosine phosphatase 1B (PTP1B). Palmitoylcarnitine suppresses protein kinase B (Akt) phosphorylation at Ser473, and this effect is not alleviated by the inhibition of PTP1B by the insulin sensitizer bis-(maltolato)-oxovanadium (IV). This result indicates that palmitoylcarnitine affects Akt activity independently of the InsR phosphorylation level. Inhibition of protein kinase C and protein phosphatase 2A does not affect the palmitoylcarnitine-mediated inhibition of Akt Ser473 phosphorylation. Additionally, palmitoylcarnitine markedly stimulates insulin release by suppressing Akt Ser473 phosphorylation in insulin-secreting RIN5F cells. In conclusion, long-chain acylcarnitines activate PTP1B and decrease InsR Tyr1151 phosphorylation and Akt Ser473 phosphorylation, thus limiting the cellular response to insulin stimulation. |
| وصف الملف: | application/pdf |
| تدمد: | 1422-0067 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7e89fcd24b4754cdc3dbd3f35b941ffdTest https://doi.org/10.3390/ijms22126470Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....7e89fcd24b4754cdc3dbd3f35b941ffd |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14220067 |
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