title: Hyperlactatemia reduces muscle glucose uptake and GLUT-4 mRNA while increasing (E1alpha)PDH gene expression in rat.
abstract: 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 (E1alpha)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.
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003847:Deoxyglucose / Q000008:administration & dosage / Q000378:metabolism; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D051275:Glucose Transporter Type 4; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D019344:Lactic Acid / Q000097:blood*; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000378:metabolism*; D011768:Pyruvate Dehydrogenase Complex / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011924:Rats, Zucker; D014316:Tritium