Alanine and Glutamine Release from the Human Forearm: Effects of Glucose Administration

Abstract

1. The effect of glucose infusion alone (175 mg/kg bolus dose followed by 4 mg min−1 kg−1 for 70 min) and in combination with forearm exercise on the exchange of glucose, alanine, glutamine and other metabolites and amino acids across forearm muscle was studied in six healthy individuals after an overnight fast. Arterial and deep venous blood was sampled and a mercury strain gauge plethysmograph was used to measure forearm blood flow. Total body energy expenditure and net glucose and fat oxidation were assessed by indirect calorimetry. 2. The infusion of glucose increased the mean arterial blood glucose concentration from 4.95 ± 0.19 (sem) to a plateau of 9.6-9.9 mmol/l (P < 0.01). The arterial blood concentrations of alanine and glutamine were not significantly altered but that of lactate increased from 0.50 ± 0.02 to 0.65 ± 0.05 mmol/l (P < 0.02) and that of pyruvate increased from 46 ± 5 to 72± 6 μmol/l (P < 0.01). In the resting state glucose administration did not significantly affect the lactate/pyruvate ratio in arterial or venous blood. Arterial plasma insulin concentration increased four-fold and total ketone body concentration decreased two- to three-fold. 3. After glucose administration, alanine release was suppressed (in all subjects) from a mean value of 153 ± 22 to 57 ± 16 nmol min−1 100 ml−1 of forearm (P < 0.02) whereas that of glutamine was not significantly affected (160 ± 30 to 143 ± 29 nmol min−1 100 ml−1 of forearm). Lactate release, like that of alanine, decreased, whereas pyruvate was slowly released in the basal state and was taken up during glucose administration (P < 0.01). These changes were associated with a decrease in the uptake of total ketone bodies to one-fifth to one-tenth of that in the basal state. 4. The net amino acid balance across the forearm muscle bed was negative throughout the study but decreased from a mean value of −567 in the basal state to −300 nmol min−1 100 ml−1 of forearm after glucose administration for 60 min. This was predominantly due to decreased release of effluxing amino acids, particularly alanine. Of those amino acids released by muscle, glutamine accounted for 25% of the molar release (36% of the amino nitrogen) in the basal state and 38% of the molar release (48% of the amino nitrogen) at the end of 60 min of glucose infusion. 5. The infusion of glucose increased energy expenditure by a mean of 2% (NS) and the respiratory exchange ratio from 0.76±0.02 to 0.82±0.02 (P < 0.02), indicating that during glucose administration about 40% of the non-protein energy expenditure was derived from net oxidation of glucose (equivalent to almost half of that infused) and the rest from oxidation of endogenous fat. 6. Intermittent isometric forearm exercise was associated with an increase in the release of lactate and pyruvate and a doubling of the lactate/pyruvate ratio in the venous blood. The release of alanine, which was previously suppressed by infusion of glucose, increased to approach that of glutamine. 7. This study demonstrates that during short-term administration of glucose, glutamine becomes the main amino acid released by muscle, carrying as much as five times more nitrogen out of muscle than alanine. The suppression of the release of alanine is paralleled by a decreased release of lactate and pyruvate and is consistent with both the activation of the pyruvate dehydrogenase complex and diversion of glucose carbon to glycogen. Most of the glucose taken up by forearm muscle appears to be converted to glycogen. During exercise there appears to be breakdown of glycogen, increased availability of lactate and pyruvate and increased release of alanine. Glutamine continues to be released at a high rate during exercise.