Impaired glucose partitioning in primary myotubes from severely obese women with type 2 diabetes
| Autor: | Pamela J. Hornby, J. Matthew Hinkley, Donghai Zheng, Walter J. Pories, Benjamin A. Kugler, James Lenhard, G. Lynis Dohm, Kai Zou, Terry E. Jones, Kristen Turner, Joseph A. Houmard |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
medicine.medical_specialty Physiology Muscle Fibers Skeletal 030209 endocrinology & metabolism Type 2 diabetes 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Humans Insulin Women Glycolysis Obesity 030212 general & internal medicine Muscle Skeletal Glycogen synthase biology Chemistry Myogenesis Skeletal muscle Cell Biology Metabolism Pyruvate dehydrogenase complex medicine.disease Citric acid cycle Glucose Endocrinology medicine.anatomical_structure Diabetes Mellitus Type 2 Case-Control Studies biology.protein Female Oxidation-Reduction Glycogen Research Article |
| Zdroj: | Am J Physiol Cell Physiol |
| ISSN: | 1522-1563 0363-6143 |
| Popis: | The purpose of this study was to determine whether intramyocellular glucose partitioning was altered in primary human myotubes derived from severely obese women with type 2 diabetes. Human skeletal muscle cells were obtained from lean nondiabetic and severely obese Caucasian females with type 2 diabetes [body mass index (BMI): 23.6 ± 2.6 vs. 48.8 ± 1.9 kg/m2, fasting glucose: 86.9 ± 1.6 vs. 135.6 ± 12.0 mg/dL, n = 9/group]. 1-[14C]-Glucose metabolism (glycogen synthesis, glucose oxidation, and nonoxidized glycolysis) and 1- and 2-[14C]-pyruvate oxidation were examined in fully differentiated myotubes under basal and insulin-stimulated conditions. Tricarboxylic acid cycle intermediates were determined via targeted metabolomics. Myotubes derived from severely obese individuals with type 2 diabetes exhibited impaired insulin-mediated glucose partitioning with reduced rates of glycogen synthesis and glucose oxidation and increased rates of nonoxidized glycolytic products, when compared with myotubes derived from the nondiabetic individuals ( P < 0.05). Both 1- and 2-[14C]-pyruvate oxidation rates were significantly blunted in myotubes from severely obese women with type 2 diabetes compared with myotubes from the nondiabetic controls. Lastly, concentrations of tricarboxylic acid cycle intermediates, namely, citrate ( P < 0.05), cis-aconitic acid ( P = 0.07), and α-ketoglutarate ( P < 0.05), were lower in myotubes from severely obese women with type 2 diabetes. These data suggest that intramyocellular insulin-mediated glucose partitioning is intrinsically altered in the skeletal muscle of severely obese women with type 2 diabetes in a manner that favors the production of glycolytic end products. Defects in pyruvate dehydrogenase and tricarboxylic acid cycle may be responsible for this metabolic derangement associated with type 2 diabetes. |
| Databáze: | OpenAIRE |
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