Glucose-lactate interrelationships: effect of ethanol

Abstract

A B S T R A C T The effect of ethanol on the interrelationship of lactate and glucose metabolism was investigated in eight human volunteers. Lactate and glucose kinetics and intervconversion rates were determined by the sequential administration of L-(+) lactate-U-14C and glucose-1-14C over an 8 hr period. After a 12 hr fast, the glucose turnover and recycling rates were 94.0 ±3.8 (SEM) and 13.7 ±1.1 mg/kg per hr, respectively. Approximately 50% of the glucose turnover or 40.7 ±2.1 mg/kg per hr was converted to lactate, accounting for 50% of the lactate turnover rate. Lactate turnover and lactate conversion to glucose were 81.8 ±6.2 and 16.7 ±1.1 mg/kg per hr, respectively. Approximately 20% of the glucose turnover was derived from lactate under these conditions. During the administration of ethanol, the blood lactate concentration doubled and the lactate turnover rate declined slightly. Lactate conversion to glucose was markedly inhibited, decreasing from 16 to 5 mg/kg per hr, and the per cent of the glucose turnover derived from lactate decreased from 18 to 6. Despite the marked inhibition of lactate conversion to glucose, neither the blood glucose concentration nor the glucose turnover rate changed. Both glucose recycling and glucose conversion to lactate were decreased, indicating that ethanol inhibited peripheral glucose utilization. There was no difference in the degree of inhibition of lactate incorporation into glucose produced by ethanol when nonfasted subjects were compared with two subjects who had fasted for 48-72 hr despite the presence of hypoglycemia in the latter.These results indicate that starvation is not a prerequisite for ethanol inhibition of gluconeogenesis from lactate in humans but is necessary for the development of hypoglycemia. Inhibition of lactate incorporation into glucose in nonfasted subjects is probably masked by a concomitant increase in glycogenolysis which prevents hypoglycemia. Ethanol decreases glucose conversion to lactate as well as lactate conversion to glucose, thus inhibiting the Cori cycle.

Modulation of red cell metabolism by states of decreased activation: Comparison between states

“…This result is consistent with relative constancy of arterial lactate during rest (Table 2) as compared with decline during TM [12], since the red cell is a primary contributor to the lactate content of blood [16]. Since total sleep and sleep stage percent were almost identical in the 2 groups, sleep cannot account for the resuits.…”

The role of adrenergic mechanisms in the substrate and hormonal response to insulin-induced hypoglycemia in man.

“…The latter iting glucose value compares favorably with studies using arteriore and atter quantitatively serial anionssayed enzyxokinase and ons per miniunting to at (production) the equations of Steele et al (30). Glucose production from alanine was estimated by a modification of the precursor-product relationships of Kreisberg et al (25). The FIGURE 4 Plasma alanine concentration (A), carbon-14 specific activity in alanine (B), and plasma alanine inflow and outflow rates before and after insulin injection (C): Alanine was quantitatively recovered from perchloric acid extracts of venous plasma by high-pressure, high-speed liquid chromatography.…”

“…The increased glucose utilization after insulin fell approxi-mately 65% in the interval [25][26][27][28][29][30] min after insulin, with a further decrease to a rate 20% less than basal 50 min after insulin. This decrease cannot be attributed solely to a decrease in circulating insulin levels, because levels of approximately 100 uU/ml were observed during this interval.…”

“…For determinations of their specific activities in plasma, glucose (25) and alanine (26) were recovered from neutralized perchloric acid extracts of blood by ion exchange chromatography techniques. Glucose was isolated by serial anion-cation exchange chromatography on Dowex 50W-X8 and AGI-X8 (Bio-Rad Laboratories, Richmond, Calif.), with recoveries between 94 and 103%o.…”

“…Precursor-product interrelationships for glucose and alanine were determined by a modification of the equations of Kreisberg et al for glucose-lactate interrelationships (25). The present modifications allow for alanine distribution in total body water (31), and correct for loss of "C label appearing in glucose, due to the fumarase randomization and subsequent decarboxylation by P-enolpyruvate carboxykinase of four-carbon intermediates in the pathway of gluconeogenesis (32,33).…”