DOSE-RESPONSE EFFECTS OF LACTATE INFUSIONS ON GLUCONEOGENESIS FROM LACTATE IN NORMAL MAN

Lactate is the predominant gluconeogenic precursor in man. To determin e the dose-response relationships between plasma lactate concentration and rates of lactate incorporation in plasma glucose (lactate glucone ogenesis, LGN), we infused 17 normal volunteers with sodium lactate fo r 180 min at rates ranging from 6 to 40 mumol kg-1 min-1 and measured [U-C-14]lactate incorporation into plasma glucose, as well as rates of lactate and glucose appearance in plasma. With the highest lactate in fusions, plasma lactate increased up to 7 mM (compared to 1.1+/-0.13 m M during control sodium bicarbonate infusions, n=10) and LGN averaged 4.73+/-0.23 mumol kg-1 min-1 (compared to 1-57+/-0.26 mumol kg-1 min-1 in bicarbonate control experiments, P<0.001). The data relating plasm a lactate concentration to LGN best fit a sigmoidal curve which platea ued at plasma lactate concentrations of approximately 6 mM and yielded an ED50 of 2.04+/-0.20 (SD) mM and a Vmax (6.25+/-1.2) (SD) (mumol kg -1 min-1). The sum of the basal rate of lactate appearance and the rat e of lactate infusion was not significantly different from the overall rates of lactate appearance during the lactate infusions (35.8+/-2.2 vs. 34.8+/-2.9 mumol kg-1 min-1, P=0.23). Thus, our results support th e view that infusion of exogenous lactate does not suppress endogenous lactate appearance in plasma.