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| Status |
Public on Dec 24, 2009 |
| Title |
Chronic hyperglycemia impairs metabolic switching of human myotubes |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Skeletal muscle of insulin resistant individuals is characterized by lower fasting lipid oxidation and reduced ability to switch between lipid and glucose oxidation. The purpose of the present study was to examine if impaired metabolic switching could be induced by chronic hyperglycemia. Human myotubes were treated with or without chronic hyperglycemia (HG) (20 mmol/l glucose for 4 days), and the metabolism of [14C]oleic acid (OA) and [14C]glucose was studied. Acute glucose (5mmol/l) suppressed OA oxidation by 50% in normoglycemic (NG) (5.5 mmol/l glucose) cells. Myotubes exposed to chronic hyperglycemia showed a significantly reduced OA uptake and oxidation to CO2, whereas acid-soluble metabolites were increased. Glucose suppressibility, the ability of acute glucose to suppress lipid oxidation, was significantly reduced to 21%, while adaptability, the capacity to increase lipid oxidation with increasing fatty acid availability, was unaffected. Glucose uptake and oxidation was significantly reduced by about 40%. Substrate oxidation in presence of mitochondrial uncouplers showed that net and maximal oxidative capacities were significantly reduced after hyperglycemia, and the concentration of ATP was reduced by 25%. However, none of the measured mitochondrial genes were downregulated nor was mitochondrial content. Microarray showed that no genes were significantly regulated by chronic hyperglycemia. Addition of chronic lactate reduced both glucose and OA oxidation to the same extent as hyperglycemia, and this effect was specific for lactate. In conclusions, chronic hyperglycemia reduced substrate oxidation in skeletal muscle cells and impaired the metabolic switching. The effect is most likely due to an induced mitochondrial dysfunction.
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| Overall design |
Cell experiment, paired observations treated vs control, cells from 3 different donors
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| Contributor(s) |
Aas V, Hessvik NP, Wettergreen M, Wensaas A, Hallén S, Thoresen GH, Rustan AC |
| Citation(s) |
20888904 |
| Submission date |
Dec 23, 2009 |
| Last update date |
Feb 18, 2019 |
| Contact name |
Hege Thoresen |
| E-mail(s) |
hege.thoresen@farmasi.uio.no
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| Phone |
+4722856555
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| Fax |
+472284402
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| Organization name |
University of Oslo
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| Department |
School of Pharmacy
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| Lab |
Dept Pharmaceutical Biosciences
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| Street address |
Sem Sælandsvei 3
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| City |
Oslo |
| ZIP/Postal code |
N-1263 |
| Country |
Norway |
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| Platforms (1) |
| GPL6884 |
Illumina HumanWG-6 v3.0 expression beadchip |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA122573 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE19620_RAW.tar |
6.3 Mb |
(http)(custom) |
TAR |
| GSE19620_non-normalized.txt.gz |
9.5 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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