Evidence for Enhanced Carrier-Mediated Hepatic Lactate Entry in Starved and Diabetic Rats

Transport of organic anions in the liver. An update on bile acid, fatty acid, monocarboxylate, anionic amino acid, cholephilic organic anion, and anionic drug transport

“…For these reasons lactic acidosis has been of major pathophysiological interest (Cohen and Woods 1983). Transmembrane transport of L-lactate was studied in anesthetized rats (Felipe et al 1991), the perfused rat liver (Sestoft and Marshall 1986;Metcalfe et al 1986), isolated rat hepatocytes (Monson et al 1982;Fafournoux et al 1985a;Metcalfe et al 1986Metcalfe et al , 1988Edlund and Halestrap 1988), and plasma membrane vesicles (Quintana et al 1988). In these studies a major problem was the extremely fast permeation and equilibration of L-lactate across the cell membrane which make it technically difficult to determine accurately uptake kinetics (Edlund and Halestrap 1988).…”

“…Whether uptake is rate limiting for lactate metabolism (Metcalfe et al 1986) or not (Edlund and Halestrap 1988;Felipe et al 1991) is controversal. Under conditions of enhanced gluconeogenesis, such as diabetes mellitus or starvation, the L-lactate transport system activity is enhanced up to 300%-400% (Metcalfe et al 1988, Felipe et al 1991. The Km value is not markedly altered under these conditions and remains at 2.2-2.4 mM.…”

Effect of weight loss on lactate transporter expression in skeletal muscle of obese subjects

“…Lactate and glucose are closely related since the former is an intermediate metabolite of the latter, and hyperlactatemia has been recognized as an independent risk factor for the development and aggravation of insulin resistance (31). Moreover, lactate is now recognized as an important substrate for ATP production in several tissues (skeletal muscles, heart, brain, and hepatocytes) (2,28). Since skeletal muscle is the tissue responsible for the vast majority of peripheral glucose uptake in response to insulin action and plays a central role in lactate metabolism, an impairment in lactate exchange in this tissue could contribute to hyperlactatemia in insulin-resistant states.…”

Further observations on the uptake and effects of phosphonates in perfused rat liver studied by31P-NMR

“…5) was an order of magnitude lower than most published estimates for the intrinsic lactate transport capacity. [16][17]44,49 Hence, only after profound inhibition can the uptake step become rate-determining with respect to intracellular lactate handling. Not unexpectedly then, we only observed a substantial depression (relatively speaking) of lactate handling at the lowest (0.3 mM) lactate level tested (Fig.…”

“…5; 0.6 AE 0.2 mM from a step-wise titration in a single liver, not shown), lower than the reported (1.9-2.5 mM) kinetic constant for hepatic lactate transport. [16][17]49 Our approach did not allow the independent determination of the intrinsic capacity of the transporter. However, the observed lactate-dependent increment in hepatic glucose output and oxygen consumption in our model (cAMP-treated liver from starved animals; estimated V max = 2.5 AE 0.3 mmol lactate equivalents/g liver/min; Fig.…”