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)PDH gene expression in rat
1 Endocrine Metabolic Laboratory, Department of Medical and Surgical Sciences, University of Padova, 35100 Padova, Italy; and 2 Centre de Recherche sur l'Endocrinologie et le Développement, Centre National de la Recherche Scientifique, 92190 Meudon-Bellevue, France
An increased basal plasma lactate concentration
is present in many physiological and pathological conditions, including
obesity and diabetes. We previously demonstrated that acute lactate
infusion in rats produced a decrease in overall glucose uptake. The
present study was carried out to further investigate the effect of
lactate on glucose transport and utilization in skeletal muscle. In
chronically catheterized rats, a 24-h sodium lactate or bicarbonate
infusion was performed. To study glucose uptake in muscle, a bolus of
2-deoxy-[3H]glucose
was injected in basal condition and during euglycemic-hyperinsulinemic clamp. Our results show that hyperlactatemia decreased glucose uptake
in muscles (i.e., red quadriceps; P < 0.05). Moreover in red muscles, both GLUT-4 mRNA (
30% in
red quadriceps and 60% in soleus;
P < 0.025) and protein (40%
in red quadriceps; P < 0.05) were
decreased, whereas the (E1
)pyruvate dehydrogenase (PDH) mRNA was
increased (+40% in red quadriceps; P < 0.001) in lactate-infused animals. PDH protein was also increased
(4-fold in red gastrocnemius and 2-fold in red quadriceps). These
results indicate that chronic hyperlactatemia reduces glucose uptake by affecting the expression of genes involved in glucose metabolism in
muscle, suggesting a role for lactate in the development of insulin resistance.
pyruvate dehydrogenase; insulin resistance; substrate competition
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