Lactate and pyruvate stimulate the conversion of glucose to glycogen in hepatocytes by a mechanism that does not involve gluconeogenic flux.
Glycogen synthesis in hepatocytes was determined at various concentrations of CO2 and medium HCO3- to modulate cell pH. Glycogen synthesis from glucose was highest in acidic conditions (5% CO2/12.5 mM HCO3-) and lowest in alkaline conditions (2.5% CO2/25 mM HCO3-). Physiological concentrations of lactate/pyruvate (2 mM/0.2 mM) stimulated the conversion of glucose to glycogen in all media examined and mercaptopicolinate, an inhibitor of gluconeogenesis, caused a similar stimulation as lactate/pyruvate. In alkaline media, the stimulation by mercaptopicolinate and by lactate/pyruvate was additive, indicating that the latter is not due to gluconeogenic flux. In acidic media, the stimulation by both lactate/pyruvate and mercaptopicolinate was inhibited by amiloride, an inhibitor of Na+/H+ exchange. Since Na+/H+ exchange is activated when cell pH falls below a certain threshold, it is postulated that lactate and pyruvate stimulate the conversion of glucose to glycogen through cellular acidification.
Tosh
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Department of Medicine, Medical School, University of Newcastle upon Tyne, UK.
Agius
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D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000096:biosynthesis*; D006863:Hydrogen-Ion Concentration; D007773:Lactates / Q000494:pharmacology*; D019344:Lactic Acid; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010848:Picolinic Acids / Q000494:pharmacology; D011773:Pyruvates / Q000494:pharmacology*; D019289:Pyruvic Acid; D051381:Rats; D017208:Rats, Wistar
D007773:Lactates; D010848:Picolinic Acids; D011773:Pyruvates; D019344:Lactic Acid; D000584:Amiloride; C008363:3-mercaptopicolinic acid; D019289:Pyruvic Acid; D006003:Glycogen; D005947:Glucose