The participation of the liver to the increase in alanine utilization seen at midpregnancy was studied in 9- and 12-day pregnant rats. Liver fractional extraction of alanine was assessed in vivo from the changes in concentration in afferent and efferent vessels. Hepatic active transport of alanine was determined in vitro using isolated plasma-membrane vesicles. Compared with nonpregnant controls, alanine fractional extraction was significantly increased on day 12 but not on day 9 of pregnancy. Vesicles isolated from 9- and 12-day pregnant animals had a greater capacity for Na+-dependent transport than those from controls. Eadie-Hofstee plotting showed that this increase was due to an increase in Vmax with no change in Km. Both A and ASC systems contributed to the Vmax increase. These results indicate that, although by day 9 the liver has developed an increased capacity for alanine uptake, the actual extraction is seen only by day 12 of pregnancy. At this stage the liver participates actively in the turnover of alanine and the development of hypoalaninemia.

In adult rats, proteins fed as a meal apart from the remainder of the diet induce alterations of protein metabolism characterized by the simultaneous stimulation of protein synthesis and breakdown. These alterations occur in parallel with an acceleration of glycogenolysis. The purpose of this work was to investigate whether these metabolic changes are related to variations in portal insulin and glucagon levels or to insulin-glucagon balance. Portal hormone concentrations, aortic glycemia and aminoacidemia, liver glycogen contents were followed over a day-night cycle in rats adapted either to mixed feeding (10% protein) or to separate feeding (protein meal given 2 hours after the onset of the light phase). Insulin and glucagon were assayed by radioimmunoassay, glucagon with antibody K 964 specific for 3500 MW glucagon. During the 3 hours following the protein meal, the portal ratio of insulin to glucagon decreased; liver glycogenolysis and glucogenic amino acid catabolism were enhanced. This glucagonotropic and glucogenic response to a protein meal administered during daytime is consistent with the increase in protein turnover previously observed. Separate feeding did not alter the overall circadian pattern of portal insulinemia which rose at night but it did alter the overall circadian pattern of portal insulinemia which rose at night but it did alter that of portal glucagonemia by maintaining it at a low level during the nightly prandial period. No correlation could be evidenced between portal insulin concentrations and the aortic levels of any amino acid in either mixed-fed or separately-fed animals. Portal glucagonemia appeared to be weakly correlated with the aortic level of arginine in both experimental groups. In the separately fed group, highly significant correlation could be evidenced between portal insulin concentrations and the aortic levels of any amino acid in either mixed-fed or separately-fed animals. Portal glucagonemia appeared to be weakly correlated with the aortic level of arginine in both experimental groups. In the separately fed group, highly significant correlations were found between portal glucagonemia and aortic concentrations of the three branched and the two aromatic amino acids.

Food intake was measured at regular intervals over 24 h in pregnant and non-pregnant female rats fed diets of different protein content: 10, 16 and 32%. During the course of pregnancy, a first period of hyperphagia was observed (days 2–12) irrespective of the composition of the diet. A second phase of hyperphagia occurred later (days 16–19) which was more marked with the better balanced diet (16% protein). During the first half of pregnancy, the increase in intake occurred principally at the beginning of the night (compensatory reaction). Later on, the stimulation extended to the last part of the night (anticipatory reaction). The nocturnal predominance of feeding activity was maintained in pregnant females in spite of their increased metabolic requirements.

A 24-hour study in rats evidenced a clear rhythmicity of both synthesis and storage of pancreatic hydrolases. Synthesis measured by incorporation of 3H leucine into proteins was maximal during the night, reaching 21.3 mg/g tissue at 2400 hours against 4.1 mg/g at 0900 hours. Amylase and chymotrypsinogen contents, on the contrary, were 2-fold higher during the day (resting period) than at night (feeding period), while trypsinogen did not vary significantly. The diametrical opposition between the variations in synthesis and enzyme contents shows that, during periods of active feeding, stimulated synthesis merely balances excretion, while during periods of spontaneous fasting, basal synthesis is greater than basal secretion resulting in a preprandial accumulation of hydrolases. The effect of dietary proteins was investigated by feeding them as a separate meal at different times of the day while providing a protein-free diet ad libitum. In this case the general pattern of synthesis was biphasic. Rates of protein synthesis increased rapidly 2- to 3-fold after the protein meal, while tissue amino acids concentrations dropped. This first peak was tentatively attributed to the action of digestive hormones released after protein ingestion. The second peak occurred 15-18 hours, later together with a rise in tissue amino-acids due to limited endogenous proteolysis. This suggests that digestive hormones and amino-acid supply act independently to stimulate the synthesis of hydrolases in the pancreas. The amount of enzyme stored depends on the timing of the protein meal with respect to the period of most intense feeding, i.e. on the timing of maximal synthesis with respect to maximal secretion.

The magnitude and composition of amino acid intestinal efflux was followed over a light-dark cycle in rats ingesting the same daily amount of protein administered either in a mixed diet (12% casein) or as a separate meal (70% casein concentrate) fed 2 hours after the onset of the light period with a protein-free diet available at all times. Intestinal efflux was determined by an instant porto-aortic difference measured on pooled samples from six rats at time-points spaced every 3 hours over a light-dark cycle. During protein digestion (dark for the mixed-fed rats) and (light for the separately-fed ones), essential amino acid composition of intestinal output fell into line with that of the protein ingested (casein) while non-essential amino acid composition did not. The discrepancy bore on alanine and glycine which were released in excess and on aspartic and glutamic acids, glutamine and serine which were released in deficit from their content in casein. From the follow-up of individual amino acid release and uptake, we concluded that intestinal efflux reflects the composition of the dietary protein only with respect to the amino acids, mostly essential, that are not metabolized by the intestinal wall.

In agreement with what is known of pancreatic adaptation to dietary composition, a progressive lowering of amylase-to-chymotrypsinogen ratio was observed in the pancreases of rats fed mixed diets of increasing casein and decreasing carbohydrate contents. The same changes in ratio were found when casein alone was increased in otherwise isonitrogenous meals fed to rats provided ad libitum with a protein-free diet. Pancreatic accumulation of chymotrypsinogen was increased while that of amylase was decreased in spite of low-protein and high-carbohydrate intakes. Lowering the lipid content of the protein-free diet reduced the effectiveness of casein meals in lowering the amylase-to-chymotrypsinogen ratio. It is concluded that 1) the capacity of protein-rich diets to induce adaptative changes in pancreatic secretion does not depend on the absolute amount of proteins passing through the duodenum but rather on the increased protein concentration in the alimentary bolus, 2) protein concentration affects both amylase and chymotrypsinogen, and 3) lipids have a cooperative effect.

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