SENP2 is vital for optimal insulin signaling and insulin-stimulated glycogen synthesis in human skeletal muscle cells
| Autor: | Medina Sistek, Stefano Bartesaghi, Hege G. Bakke, Xiao-Rong Peng, Eili Tranheim Kase, G. Hege Thoresen, Solveig A. Krapf, Jenny Lund, Arild C. Rustan |
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| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
medicine.medical_treatment Glucose uptake RM1-950 Carbohydrate metabolism SENP2 Internal medicine medicine Glycogen synthase Beta oxidation General Environmental Science biology Chemistry Myogenesis Insulin Lentivirus Skeletal muscle Energy metabolism Primary human myotubes Insulin sensitivity Insulin receptor Endocrinology medicine.anatomical_structure biology.protein General Earth and Planetary Sciences Therapeutics. Pharmacology Knockdown Research Paper |
| Zdroj: | Current Research in Pharmacology and Drug Discovery Current Research in Pharmacology and Drug Discovery, Vol 2, Iss, Pp 100061-(2021) |
| ISSN: | 2590-2571 |
| DOI: | 10.1016/j.crphar.2021.100061 |
| Popis: | Sentrin-specific protease (SENP) 2 has been suggested as a possible novel drug target for the treatment of obesity and type 2 diabetes mellitus after observations of a palmitate-induced increase in SENP2 that lead to increased fatty acid oxidation and improved insulin sensitivity in skeletal muscle cells from mice. However, no precedent research has examined the role of SENP2 in human skeletal muscle cells. In the present work, we have investigated the impact of SENP2 on fatty acid and glucose metabolism as well as insulin sensitivity in human skeletal muscle using cultured primary human myotubes. Acute (4 h) oleic acid oxidation was reduced in SENP2-knockdown (SENP2-KD) cells compared to control cells, with no difference in uptake. After prelabeling (24 h) with oleic acid, total lipid content and incorporation into triacylglycerol was decreased, while incorporation into other lipids, as well as complete oxidation and β-oxidation was increased in SENP2-KD cells. Basal glucose uptake (i.e., not under insulin-stimulated conditions) was higher in SENP2-KD cells, whereas oxidation was similar to control myotubes. Further, basal glycogen synthesis was not different in SENP2-KD myotubes, but both insulin-stimulated glycogen synthesis and AktSer473 phosphorylation was completely blunted in SENP2-KD cells. In conclusion, SENP2 plays an important role in fatty acid and glucose metabolism in human myotubes. Interestingly, it also appears to have a pivotal role in regulating myotube insulin sensitivity. Future studies should examine the role of SENP2 in regulation of insulin sensitivity in other tissues and in vivo, defining the potential for SENP2 as a drug target. Graphical abstract Image 1 Highlights • SENP2 play an important role in glucose metabolism in human myotubes. • SENP2 has a pivotal role in lipid metabolism in human myotubes. • SENP2 appears to have a critical role in myotubes insulin sensitivity. |
| Databáze: | OpenAIRE |
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