Abstract | BACKGROUND: METHODS: RESULTS: Our 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. CONCLUSION:
Myriocin 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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Authors | Agnieszka Mikłosz, Bartłomiej Łukaszuk, Marcin Baranowski, Jan Górski, Adrian Chabowski |
Journal | PloS one
(PLoS One)
Vol. 8
Issue 12
Pg. e85547
( 2013)
ISSN: 1932-6203 [Electronic] United States |
PMID | 24376889
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 4-(4-(4-chloro-phenyl)thiazol-2-ylamino)phenol
- Fatty Acids, Monounsaturated
- Palmitates
- Thiazoles
- Deoxyglucose
- Serine C-Palmitoyltransferase
- Phosphotransferases (Alcohol Group Acceptor)
- sphingosine kinase
- thermozymocidin
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Topics |
- Analysis of Variance
- Animals
- Blotting, Western
- Chromatography, High Pressure Liquid
- Deoxyglucose
(metabolism)
- Fatty Acids, Monounsaturated
(pharmacology)
- Insulin Resistance
(physiology)
- Muscle Fibers, Skeletal
(metabolism, physiology)
- Palmitates
(pharmacology)
- Phosphotransferases (Alcohol Group Acceptor)
(antagonists & inhibitors)
- Rats
- Serine C-Palmitoyltransferase
(antagonists & inhibitors)
- Thiazoles
(pharmacology)
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