Abstract
Previous studies have shown that chronic hyperglycemia impairs glucose and fatty acid oxidation in cultured human myotubes. To further study the hyperglycemia-induced suppression of oxidation, lactate oxidation, mitochondrial function and glycolytic rate were evaluated. Further, we examined the intracellular content of reactive oxygen species (ROS), production of lactate and conducted pathway-ANOVA analysis on microarray data. In addition, the roles of the pentose phosphate pathway (PPP) and the hexosamine pathway were evaluated. Lactic acid oxidation was suppressed in hyperglycemic versus normoglycaemic myotubes. No changes in mitochondrial function or ROS concentration were observed. Pathway-ANOVA analysis indicated several upregulated pathways in hyperglycemic cells, including glycolysis and PPP. Functional studies showed that glycolysis and lactate production were higher in hyperglycemic than normoglycaemic cells. However, there were no indications of involvement of PPP or the hexosamine pathway. In conclusion, hyperglycemia reduced substrate oxidation while increasing glycolysis and lactate production in cultured human myotubes.
Highlights
Sustained hyperglycemia in patients with metabolic syndrome contributes both to the diabetic state and to diabetic complications [1,2,3,4]
As it may be hypothesized that chronic hyperglycemia may induce hypertonicity in the medium, we explored this possibility by comparing NG with normal HG induced by d-glucose, HG induced by l-glucose, and similar concentration of mannitol (15 mM) on glucose uptake and oxidation in the myotubes
Mean lactic acid oxidation was reduced by 31% in myotubes treated with HG compared to NG
Summary
Sustained hyperglycemia in patients with metabolic syndrome contributes both to the diabetic state and to diabetic complications [1,2,3,4]. This glucose toxicity is thought to be mediated by an increased flux of glucose through the glycolytic pathway, generation of glycosylated proteins, and reactive oxygen species (ROS) [5]. We observed that the addition of lactate to the cells induced similar effects as hyperglycemia on glucose and oleic acid (OA). This effect of lactate was specific, as other acids that lowered pH to the same extent did not affect glucose and OA metabolism. Increased production of lactate could be a factor in the
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