ArticlePloS one2013
Effects of inhibition of serine palmitoyltransferase (SPT) and sphingosine kinase 1 (SphK1) on palmitate induced insulin resistance in L6 myotubes.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 31 citations in OpenAlex.
- Ceramides as Biomarkers of Cardiovascular Diseases and Heart Failure.Current heart failure reports · 2024Review
- Article
- CHO/LY-B cell growth under limiting sphingolipid supply: Correlation between lipid composition and biophysical properties of sphingolipid-restricted cell membranes.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Role of Sphingosine Kinase in Type 2 Diabetes Mellitus.Frontiers in endocrinology · 2020Review
- Sphingolipid Metabolism and Signaling in Skeletal Muscle: From Physiology to Physiopathology.Frontiers in endocrinology · 2020Review
- Dose- and time-dependent alterations in lipid metabolism after pharmacological PGC-1α activation in L6 myotubes.Journal of cellular physiology · 2019Article
- Sphingolipid changes do not underlie fatty acid-evoked GLUT4 insulin resistance nor inflammation signals in muscle cells.Journal of lipid research · 2018Article
- Palmitate- and C6 ceramide-inducedNutrition & metabolism · 2018Article
- The role of sphingolipid signalling in diabetes‑associated pathologies (Review).International journal of molecular medicine · 2017Review
- A pilot study examining the impact of exercise training on skeletal muscle genes related to the TLR signaling pathway in older adults following hip fracture recovery.Journal of applied physiology (Bethesda, Md. : 1985) · 2017Article
- Effect of plasma free fatty acid supply on the rate of ceramide synthesis in different muscle types in the rat.PloS one · 2017Article
- Changes in the Diaphragm Lipid Content after Administration of Streptozotocin and High-Fat Diet Regime.Journal of diabetes research · 2017Article
- Direct and maternal n-3 long-chain polyunsaturated fatty acid supplementation improved triglyceridemia and glycemia through the regulation of hepatic and muscle sphingolipid synthesis in offspring hamsters fed a high-fat diet.European journal of nutrition · 2016Article
- Insulin Resistance and Obesity Affect Lipid Profile in the Salivary Glands.Journal of diabetes research · 2016Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe objective of this study was to examine the effects of short (2 h) and prolonged (18 h) inhibition of serine palmitoyltransferase (SPT) and sphingosine kinase 1 (SphK1) on palmitate (PA) induced insulin resistance in L6 myotubes.
methodsL6 myotubes were treated simultaneously with either PA and myriocin (SPT inhibitor) or PA and Ski II (SphK1inhibitor) for different time periods (2 h and 18 h). Insulin stimulated glucose uptake was measured using radioactive isotope. Expression of insulin signaling proteins was determined using Western blot analyses. Intracellular sphingolipids content [sphinganine (SFA), ceramide (CER), sphingosine (SFO), sphingosine-1-phosphate (S1P)] were estimated by HPLC.
resultsOur results revealed that both short and prolonged time of inhibition of SPT by myriocin was sufficient to prevent ceramide accumulation and simultaneously reverse palmitate induced inhibition of insulin-stimulated glucose transport. In contrast, prolonged inhibition of SphK1 intensified the effect of PA on insulin-stimulated glucose uptake and attenuated further the activity of insulin signaling proteins (pGSK3β/GSK3β ratio) in L6 myotubes. These effects were related to the accumulation of sphingosine in palmitate treated myotubes.
conclusionMyriocin is more effective in restoration of palmitate induced insulin resistance in L6 myocytes, despite of the time of SPT inhibition, comparing to SKII (a specific SphK1 inhibitor). Observed changes in insulin signaling proteins were related to the content of specific sphingolipids, namely to the reduction of ceramide. Interestingly, inactivation of SphK1 augmented the effect of PA induced insulin resistance in L6 myotubes, which was associated with further inhibition of insulin stimulated PKB and GSK3β phosphorylation, glucose uptake and the accumulation of sphingosine.
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