SENP2 is vital for optimal insulin signaling and insulin-stimulated glycogen synthesis in human skeletal muscle cells
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...
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doaj-1aefb167ef6a43069d7e66d63da000b82021-10-03T04:43:57ZengElsevierCurrent Research in Pharmacology and Drug Discovery2590-25712021-01-012100061SENP2 is vital for optimal insulin signaling and insulin-stimulated glycogen synthesis in human skeletal muscle cellsJenny Lund0Solveig A. Krapf1Medina Sistek2Hege G. Bakke3Stefano Bartesaghi4Xiao-Rong Peng5Arild C. Rustan6G. Hege Thoresen7Eili T. Kase8Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, Norway; Corresponding author. Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, P.O. Box 1068 Blindern, 0316 Oslo, Norway.Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, NorwaySection for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, NorwaySection for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, NorwayBioscience Metabolism, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM) BioPharmaceuticals R&D, AstraZeneca, Gothenburg, SwedenBioscience Metabolism, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM) BioPharmaceuticals R&D, AstraZeneca, Gothenburg, SwedenSection for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, NorwaySection for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, Norway; Department of Pharmacology, Institute of Clinical Medicine, University of Oslo, NorwaySection for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, NorwaySentrin-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.http://www.sciencedirect.com/science/article/pii/S2590257121000481SENP2LentivirusKnockdownPrimary human myotubesEnergy metabolismInsulin sensitivity |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jenny Lund Solveig A. Krapf Medina Sistek Hege G. Bakke Stefano Bartesaghi Xiao-Rong Peng Arild C. Rustan G. Hege Thoresen Eili T. Kase |
spellingShingle |
Jenny Lund Solveig A. Krapf Medina Sistek Hege G. Bakke Stefano Bartesaghi Xiao-Rong Peng Arild C. Rustan G. Hege Thoresen Eili T. Kase SENP2 is vital for optimal insulin signaling and insulin-stimulated glycogen synthesis in human skeletal muscle cells Current Research in Pharmacology and Drug Discovery SENP2 Lentivirus Knockdown Primary human myotubes Energy metabolism Insulin sensitivity |
author_facet |
Jenny Lund Solveig A. Krapf Medina Sistek Hege G. Bakke Stefano Bartesaghi Xiao-Rong Peng Arild C. Rustan G. Hege Thoresen Eili T. Kase |
author_sort |
Jenny Lund |
title |
SENP2 is vital for optimal insulin signaling and insulin-stimulated glycogen synthesis in human skeletal muscle cells |
title_short |
SENP2 is vital for optimal insulin signaling and insulin-stimulated glycogen synthesis in human skeletal muscle cells |
title_full |
SENP2 is vital for optimal insulin signaling and insulin-stimulated glycogen synthesis in human skeletal muscle cells |
title_fullStr |
SENP2 is vital for optimal insulin signaling and insulin-stimulated glycogen synthesis in human skeletal muscle cells |
title_full_unstemmed |
SENP2 is vital for optimal insulin signaling and insulin-stimulated glycogen synthesis in human skeletal muscle cells |
title_sort |
senp2 is vital for optimal insulin signaling and insulin-stimulated glycogen synthesis in human skeletal muscle cells |
publisher |
Elsevier |
series |
Current Research in Pharmacology and Drug Discovery |
issn |
2590-2571 |
publishDate |
2021-01-01 |
description |
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. |
topic |
SENP2 Lentivirus Knockdown Primary human myotubes Energy metabolism Insulin sensitivity |
url |
http://www.sciencedirect.com/science/article/pii/S2590257121000481 |
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