Regulation of plasma lactate concentration in resting human subjects

We evaluated the relative contributions of glucose, insulin, and the rate of glucose disposal to the regulation of the plasma lactate concentration. Rates of glucose disposal were measured in 88 separate studies in whole body and across the forearm at varying plasma insulin (9, 50, 160, and 1,800 microU/mL) concentrations, and at each insulin concentration at four different glucose concentrations (90, 160, 250, and 400 mg/dL) in healthy male subjects. The rate of glucose disposal was positively correlated with the plasma lactate concentration (r = .83, n = 88, P less than .0001). When the plasma lactate concentration was adjusted for the rate of glucose disposal, plasma glucose or insulin concentrations did not contribute significantly to the residual variation in plasma lactate. When plasma lactate concentrations were compared at matched rates of glucose disposal, the lactate levels were similar regardless of whether glucose disposal was induced by hyperglycemia or hyperinsulinemia. At the lowest glucose and insulin concentrations, forearm tissues released lactate, but at all other glucose and insulin concentrations, no significant net lactate flux was observed. After subtraction of the rate of forearm glucose disposal from whole-body glucose disposal, the plasma lactate concentration correlated with the remaining, extramuscular, rate of glucose disposal (r = .60, P less than .0001). These data suggest that in resting normal subjects the plasma lactate concentration may be determined by the rate of glucose disposal in extramuscular tissues, rather than the ambient glucose or insulin concentration.