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Tytuł pozycji:

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

Tytuł :
Impaired glucose partitioning in primary myotubes from severely obese women with type 2 diabetes.
Autorzy :
Kai Zou
Turner, Kristen
Donghai Zheng
Hinkley, J. Matthew
Kugler, Benjamin A.
Hornby, Pamela J.
Lenhard, James
Jones, Terry E.
Pories, Walter J.
Dohm, G. Lynis
Houmard, Joseph A.
Pokaż więcej
Temat :
TYPE 2 diabetes
OVERWEIGHT women
PYRUVATES
GLYCOLYSIS
KREBS cycle
GLUCOSE
GLUCOSE synthesis
Źródło :
American Journal of Physiology: Cell Physiology; Dec2020, Vol. 319 Issue 6, pC1011-C1019, 9p
Czasopismo naukowe
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. [ABSTRACT FROM AUTHOR]
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