RESUMEN
Lactate, a product of glycolysis, is formed under aerobic conditions. Extensive work has shown lactate flux in young and exercising humans; however, the effect of age is not known. We tested the hypothesis that postprandial lactate shuttling (PLS) would be diminished in older adults. We used [3-13C]lactate and [6,6-2H]-glucose tracers, an OGTT, and arterialized blood sampling to determine postprandial lactate rates of appearance (Ra), disappearance (Rd), and oxidation (Rox) in 15 young (28.1 ± 1.4 yr) and 13 older (70.6 ± 2.4 yr) healthy men and women. In young participants fasting blood [lactate] [¼ 0.5 mM] rose after the glucose challenge, peaked at 15 min, dipped to a nadir at 30 min, and rose again peaking at 60 min [¼ 1.0mM]. Initial responses in lactate Ra of older participants were delayed and diminished until 90 minutes rising by 0.83 mg·kg-1·min-1. Lactate Rox was higher throughout the entire trial in young participants by a difference of approximately 0.5 mg·kg-1·min-1. Initial peaks in lactate Ra and concentration in all volunteers demonstrated presence of an enteric PLS following an OGTT. Notably, in the systemic, but not enteric PLS phase, lactate Ra correlated highly with glucose Rd (r2 = 0.92). Correspondence of second peaks in lactate Ra and concentration and glucose Rd show dependence of lactate Ra on glucose Rd. While results show both enteric and systemic PLS phases in young and older study cohorts, metabolic responses were delayed and diminished in healthy older individuals.
RESUMEN
Our purpose was to determine how age affects metabolic flexibility and underlying glucose kinetics in healthy young and older adults. Therefore, glucose and lactate tracers along with pulmonary gas exchange data were used to determine glucose kinetics and respiratory exchange ratios [RER = carbon dioxide production (VÌco2)/oxygen consumption (VÌo2)] during a 2-h 75-g oral glucose tolerance test (OGTT). After an 12-h overnight fast, 28 participants, 15 young (21-35 yr; 7 men and 8 women) and 13 older (60-80 yr; 7 men and 6 women), received venous primed-continuous infusions of [6,6-2H]glucose and [3-13C]lactate with a [Formula: see text] bolus. After a 90-min metabolic stabilization and tracer equilibration period, volunteers underwent an OGTT. Arterialized glucose concentrations ([glucose]) started to rise 15 min post glucose consumption, peaked at 60 min, and remained elevated. As assessed by rates of appearance (Ra) and disposal (Rd) and metabolic clearance rate (MCR), glucose kinetics were suppressed in older compared to young individuals. As well, unlike in young individuals, fractional gluconeogenesis (fGNG) remained elevated in the older population after the oral glucose challenge. Finally, there were no differences in 12-h fasting baseline or peak RER values following an oral glucose challenge in older compared to young men and women, making RER an incomplete measure of metabolic flexibility in the volunteers we evaluated. Our study revealed that glucose kinetics are significantly altered in a healthy aged population after a glucose challenge. Furthermore, those physiological deficits are not detected from changes in RER during an OGTT.NEW & NOTEWORTHY To determine metabolic flexibility in response to an OGTT, we studied healthy young and older men and women to determine glucose kinetics and changes in RER. Compared to young subjects, glucose kinetics were suppressed in older healthy individuals during an OGTT. Surprisingly, the age-related changes in glucose flux were not reflected in RER measurements; thus, RER measurements do not give a complete view of metabolic flexibility in healthy individuals.
Asunto(s)
Envejecimiento , Glucemia , Prueba de Tolerancia a la Glucosa , Glucosa , Humanos , Femenino , Masculino , Adulto , Anciano , Persona de Mediana Edad , Envejecimiento/metabolismo , Envejecimiento/fisiología , Glucosa/metabolismo , Adulto Joven , Anciano de 80 o más Años , Glucemia/metabolismo , Cinética , Consumo de Oxígeno/fisiología , Gluconeogénesis/fisiología , Ácido Láctico/metabolismo , Ácido Láctico/sangre , Intercambio Gaseoso Pulmonar/fisiología , Tasa de Depuración MetabólicaRESUMEN
Dietary glucose in excess is stored in the liver in the form of glycogen. As opposed to direct conversion of glucose into glycogen, the hypothesis of the postprandial lactate shuttle (PLS) proposes that dietary glucose uptake is metabolized to lactate in the gut, thereby being transferred to the liver for glycogen storage. In the present study, we provide evidence of a PLS in young healthy men and women. Overnight fasted participants underwent an oral glucose tolerance test, and arterialized lactate concentration and rate of appearance were determined. The concentration of lactate in the blood rose before the concentration of glucose, thus providing evidence of an enteric PLS. Secondary increments in the concentration of lactate in the blood and its rate of appearance coincided with those of glucose, which indicates the presence of a larger, secondary, systemic PLS phase driven by hepatic glucose release. The present study challenges the notion that lactate production is the result of hypoxia in skeletal muscles, because our work indicates that glycolysis proceeds to lactate in fully aerobic tissues and dietary carbohydrate is processed via lactate shuttling. Our study proposes that, in humans, lactate is a major vehicle for carbohydrate carbon distribution and metabolism.