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Impaired glucose partitioning in primary myotubes from severely obese women with type 2 diabetes
Journal article   Open access   Peer reviewed

Impaired glucose partitioning in primary myotubes from severely obese women with type 2 diabetes

Kai Zou, Kristen Turner, Donghai Zheng, J Matthew Hinkley, Benjamin A Kugler, Pamela J Hornby, James Lenhard, Terry E Jones, Walter J Pories, G Lynis Dohm, …
American Journal of Physiology: Cell Physiology, v 319(6), pp C1011-C1019
01 Dec 2020
DOI: https://doi.org/10.1152/ajpcell.00157.2020
PMID: 32966127
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792675View
Published, Version of Record (VoR)Open Access (License Unspecified),  Open

Abstract

Adult Case-Control Studies Diabetes Mellitus, Type 2 - metabolism Female Glucose - metabolism Glycogen - metabolism Glycolysis - physiology Humans Insulin - metabolism Muscle Fibers, Skeletal - metabolism Muscle, Skeletal - metabolism Obesity - metabolism Oxidation-Reduction Women
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/m , fasting glucose: 86.9 ± 1.6 vs. 135.6 ± 12.0 mg/dL, = 9/group]. 1-[ C]-Glucose metabolism (glycogen synthesis, glucose oxidation, and nonoxidized glycolysis) and 1- and 2-[ C]-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 ( < 0.05). Both 1- and 2-[ C]-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 ( < 0.05), cis-aconitic acid ( = 0.07), and α-ketoglutarate ( < 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.

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Collaboration types
Industry collaboration
Domestic collaboration
Web of Science research areas
Cell Biology
Physiology
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