Lactate flux and gluconeogenesis in fasting, weaned northern elephant seals (Mirounga angustirostris)

Elephant seals maintain rates of endogenous glucose production (EGP) typical of post-absorptive mammals despite enduring prolonged periods of food deprivation concurrent with low rates of glucose oxidation. These high rates of EGP suggest extensive glucose recycling during fasting. We investigated lactate metabolism in fasting elephant seals to assess its role in glucose recycling. Whole-animal glucose and lactate fluxes were measured as the rates of appearance of glucose and lactate (Ra gluc and Ra lac, respectively) using a primed constant infusion of [U-(14)C] lactate and [6-(3)H] glucose, and we calculated the minimum contribution of lactate to gluconeogenesis (GNG lac). Ra lac was high compared to resting values in other species (3.21 ± 0.71 mmol min(-1)* kg(-1)), did not change between 14 ± 1 and 31 ± 8 days of fasting and varied directly with Ra glu. The minimum GNG lac was 44.6 ± 6.0% of EGP, varied directly with plasma lactate levels, and did not change over the fast. Ra lac and Ra glu both varied directly with plasma insulin concentrations. These data suggest that lactate is the predominant gluconeogenic precursor in fasting elephant seals and that high rates of glucose recycling through Cori cycle activity contribute to the maintenance of EGP during fasting. High levels of Cori cycle activity and EGP may be important components of metabolic adaptations that maintain glucose production while avoiding ketosis during extended fasting or are related to sustained metabolic alterations associated with extended breath-holds in elephant seals.