scholarly journals Effect of L-alanine infusion on gluconeogenesis and ketogenesis in the rat in vivo

1978 ◽  
Vol 170 (3) ◽  
pp. 583-591 ◽  
Author(s):  
P T Ozand ◽  
W D Reed ◽  
R L Hawkins ◽  
J H Stevenson ◽  
J T Tildon ◽  
...  

1. In 48 h-starved 6-week-old rats the 14C incorporation in vivo into blood glucose from a constant-specific-radioactivity pool of circulating [14c]actateconfirmed that lactate is the preferred gluconeogenic substrate. 2. Increasing the blood [alanine] to that occurrring in the fed state increased 14C incorporation into blood glucose 2.3-fold from [14c]alanine and 1.7-fold from [14c]lactate. 3. When the blood [alanine] was increased to that in the fed state, the 14C incorporation into liver glycogen from circulating [14c]alanine or [14c]lactate increased 13.5- and 1.7-fold respectively. 4. The incorporation of 14C into blood acetoacetate and 3-hydroxybutyrate from a constant-specific-radioactivity pool of circulating [14c]oleate was virtually abolished by increasing the blood [alanine] to that existing in the fed state. However, the [acetoacetate] remained unchanged, whereas [3-hydroxybutyrate] decreased, although less rapidly than did its radiochemical concentration. 5. It is concluded that during starvation in 6-week-old rats, the blood [alanine] appears to influence ketogenesis for circulating unesterfied fatty acids and inversely affects gluconeogenesis from either lactate or alanine. A different pattern of gluconeogenesis may exist for alanine and lactate as evidenced by comparative 14C incorporation into liver glycogen and blood glucose.

1979 ◽  
Vol 182 (2) ◽  
pp. 565-575 ◽  
Author(s):  
F Okajima ◽  
M Ui

1. A trace amount of glucose labelled with 14C uniformly and with 3H at position 2, 3 or 6 was injected intravenously into starved rats to measure the turnover rate of blood glucose. 2. Reliable estimates were made based on the semilogarithmic plot of specific radioactivity of the glucose contained in whole blood samples taken from the tail vein. 3. Glucose turned over more rapidly in hyperthyroid and more slowly in hypothyroid than in euthyroid rats. The percentage contribution of glucose recycling (determined from the difference in replacement rates between [U-14C]glucose and [6-3H]glucose) to the glucose utilization increased on induction of hyperthyroidism. 4. Futile cycles between glucose and glucose 6-phosphate (determined from the difference between replacement rates of [2-3H]glucose and [6-3H]glucose) were activated and inactivated by induction of hyperthyroid and hypothyroid states respectively. 5. The hepatic content of glycogen was much lower in hyper- and hypo-thyroid than in euthyroid rats. The enhanced glucose production in hyperthyroid rats resulted from not only activationof hepatic gluconeogenesis but also diversion of the final product of gluconeogenesis from liver glycogen to blood glucose. In hypothyroidism, the inhibition of gluconeogensis led to suppression of both glucose production and glycogenesis in the liver.


1972 ◽  
Vol 127 (3) ◽  
pp. 521-529 ◽  
Author(s):  
Richard G. Vernon ◽  
Deryck G. Walker

1. The specific radioactivity of plasma d-glucose and the incorporation of 14C into plasma l-lactate, liver glycogen and skeletal-muscle glycogen was measured as a function of time after the intraperitoneal injection of d-[6-14C]glucose and d-[6-3H]glucose into newborn, 2-, 10- and 30-day-old rats. 2. The log of the specific radioactivity of both plasma d-[6-14C]- and d-[6-3H]-glucose of the 2-, 10- and 30-day-old rats decreased linearly with time for at least 60min after injection of labelled glucose. The specific radioactivity of both plasma d-[6-14C]- and d-[6-3H]-glucose of the newborn rat remained constant for at least 75min after injection. 3. The glucose turnover rate of the 30-day-old rat was significantly greater than (approximately twice) that of the 2- and 10-day-old rats. The relative size of both the glucose pool and the glucose space decreased with age. Less than 10% of the glucose utilized in the 2-, 10- and 30-day-old rats was recycled via the Cori cycle. 4. The results are discussed in relationship to the availability of dietary glucose and other factors that may influence glucose metabolism in the developing rat.


1972 ◽  
Vol 127 (3) ◽  
pp. 531-537 ◽  
Author(s):  
Richard G. Vernon ◽  
Deryck G. Walker

1. The specific radioactivity of plasma l-lactate and the incorporation of 14C into plasma d-glucose, liver glycogen and skeletal-muscle glycogen were measured as a function of time after the intraperitoneal injection of l-[U-14C]lactate into 2-, 10- and 30-day-old rats. 2. Between 15 and 60min after the injection of the l-[U-14C]lactate, the specific radioactivity of plasma lactate decreased with a half-life of 20–33min in animals at all three ages. 3. At all times after injection examined, the specific radioactivity of plasma glucose of the 2- and 10-day-old rats was at least fourfold greater than that of the 30-day-old rats. 4. Although 14C was incorporated into liver glycogen the amount incorporated was always less than 5% of that present in plasma glucose. 5. The results are discussed with reference to the factors that may influence the rate of incorporation of 14C into plasma glucose, and it is concluded that the rate of gluconeogenesis in the 2- and 10-day-old suckling rat is at least twice that of the weaned 30-day-old animal.


1993 ◽  
Vol 265 (2) ◽  
pp. R334-R340 ◽  
Author(s):  
T. A. Davis ◽  
M. L. Fiorotto ◽  
H. V. Nguyen ◽  
P. J. Reeds

To compare the sensitivity of muscle protein synthesis to food intake in neonatal and weaned rats, 5- and 16-day-old suckled rats and 28-day-old weaned rats were either fed, fasted for 8-10 h, or refed for 1-4 h after an 8-h fast. Protein synthesis was measured in vivo in soleus and plantaris muscles with a large dose of L-[4-3H]phenylalanine. In fed rats, fractional rates of protein synthesis (KS) decreased with age. Fasting decreased KS, and refeeding increased KS most in 5-day-old animals, less in 16-day-old rats, and least in 28-day-old rats. In 5-day-old rats, there were no differences in KS between soleus and plantaris muscles in the fed state and after fasting and refeeding; at 28 days, KS was higher in soleus than in plantaris in fed rats, and the soleus did not respond to fasting and refeeding. In rats at all three ages, the concentration of most plasma amino acids decreased during fasting; when 5-day-old rats were refed, plasma amino acid concentrations increased, but not to the levels in the fed state. Plasma insulin concentrations increased with age. Plasma insulin concentrations decreased more rapidly with fasting and increased more extensively with refeeding in 5-day-old rats than in older rats. These results suggest that muscle protein synthesis is more responsive to food intake in young suckled rats than in older suckled or weaned rats; this increased responsiveness is accompanied by greater changes in circulating insulin concentrations.


1973 ◽  
Vol 134 (4) ◽  
pp. 899-906 ◽  
Author(s):  
Keith Snell ◽  
Deryck G. Walker

1. The concentrations of liver glycogen and plasma d-glucose were measured in caesarian-delivered newborn rats at time-intervals up to 3h after delivery after treatment of the neonatal rats with glucagon, dibutyryl cyclic AMP, cortisol or cortisol+dibutyryl cyclic AMP. Glycogenolysis was promoted by glucagon or dibutyryl cyclic AMP in the third hour after birth but not at earlier times. Cortisol and dibutyryl cyclic AMP together (but neither agent alone) promoted glycogenolysis in the second hour after birth, but no hormone combination was effective in the first postnatal hour. 2. The specific radioactivity of plasma d-glucose was measured as a function of time for up to 75 min after the intraperitoneal injection of d-[6-14C]glucose and d-[6-3H]glucose into newborn rats at delivery and after treatment with glucagon or actinomycin D. Glucagon-mediated hyperglycaemia at this time was due to an increased rate of glucose formation and a decreased rate of glucose utilization. Actinomycin D prevented glucose formation and accelerated the rate of postnatal hypoglycaemia. 3. The specific radioactivity of plasma l-lactate and the incorporation of 14C into plasma d-glucose was measured as a function of time after the intraperitoneal injection of l-[U-14C]lactate into glucagon- or actinomycin D-treated rats immediately after delivery. The calculated rates of lactate formation were unchanged by either treatment, but lactate utilization was stimulated by glucagon administration. Glucagon stimulated and actinomycin D diminished 14C incorporation into plasma d-glucose. 4. The factors involved in the initiation of glycogenolysis and gluconeogenesis in the rat immediately after birth are discussed.


1993 ◽  
Vol 290 (1) ◽  
pp. 67-73 ◽  
Author(s):  
G C Burdge ◽  
F J Kelly ◽  
A D Postle

Hepatic phosphatidylcholine (PC) from the immature fetal guinea pig at day 55 of gestation comprised mainly unsaturated molecular species containing C18:2(n-6) and C22:6(n-3) at the sn-2 position, reflecting placental permeability to essential fatty acids. At both day 55 and term (day 68), [Me-14C]choline was incorporated in utero over 3 h largely into sn-1-C16:0 PC species, with incorporation into sn-1-C18:0 PC species increasing by 18 h of incubation. Comparison of specific radioactivities after 3 h and 18 h suggests PC acyl remodelling by phospholipase A1. No incorporation into C20:4(n-6)-containing PC species could be detected of either [Me-14C]choline in vivo or CDP-[Me-14C]choline in isolated microsomes. The major phosphatidylethanolamine (PE) species were 16:0/22:6 and 18:0/22:6. Although [14C]ethanolamine was initially incorporated mainly into sn-1-C16:0 species, specific-radioactivity analysis suggested differential turnover rather than acyl remodelling. [1,2-14C]Ethanolamine and [Me-14C]methionine incorporation into PC molecular species indicated that both newly synthesized and total PE pools were available for N-methylation. Since the PC pool synthesized from PE included C20:4- and C22:6-containing species, N-methylation may provide a mechanism for supplying essential long-chain fatty acids to developing tissues that can be regulated independently from bulk PC synthesis.


1998 ◽  
Vol 95 (4) ◽  
pp. 1776-1781 ◽  
Author(s):  
W. H. Martin ◽  
D. J. Hoover ◽  
S. J. Armento ◽  
I. A. Stock ◽  
R. K. McPherson ◽  
...  

2005 ◽  
Vol 288 (1) ◽  
pp. E187-E193 ◽  
Author(s):  
Rachel A. Baar ◽  
Carlus S. Dingfelder ◽  
Lisa A. Smith ◽  
David A. Bernlohr ◽  
Chaodong Wu ◽  
...  

The metabolic impact of the murine adipocyte fatty acid-binding protein (AFABP/aP2) on lipid metabolism was investigated in the AFABP/aP2−/− mouse and compared with wild-type C57BL/6J littermates. Mice were weaned on a high-fat diet (59% of energy from fat) and acclimated to meal feeding. Stable isotopes were administered, and indirect calorimetry was performed to quantitate fatty acid flux, dietary fatty acid utilization, and substrate oxidation. Consistent with previous in situ and in vitro studies, fasting serum nonesterified fatty acid (NEFA) release was significantly reduced in AFABP/aP2−/− (17.1 ± 9.0 vs. 51.9 ± 22.9 mg·kg−1·min−1). AFABP/aP2−/− exhibited higher serum NEFA (1.4 ± 0.6 vs. 0.8 ± 0.4 mmol/l, AFABP/aP2−/− vs. C57BL/6J, respectively) and triacylglycerol (TAG; 0.23 ± 0.09 vs. 0.13 ± 0.10 mmol/l) and accumulated more TAG in liver tissue (2.9 ± 2.3 vs. 1.1 ± 0.8% wet wt) in the fasted state. For the liver-TAG pool, 16.4 ± 7.3% of TAG-fatty acids were derived from serum NEFA in AFABP/aP2−/−. In contrast, a significantly greater portion of C57BL/6J liver-TAG was derived from serum NEFA (42.3 ± 25.5%) during tracer infusion. For adipose-TAG stores, only 0.29 ± 0.04% was derived from serum NEFA in AFABP/aP2−/−, and, in C57BL/6J, 1.85 ± 0.97% of adipose-TAG was derived from NEFA. In addition, AFABP/aP2−/− preferentially oxidized glucose relative to fatty acids in the fed state. These data demonstrate that in vivo disruption of AFABP/aP2−/− leads to changes in the following two major metabolic processes: 1) decreased adipose NEFA efflux and 2) preferential utilization of glucose relative to fatty acids.


1988 ◽  
Vol 255 (3) ◽  
pp. 929-935 ◽  
Author(s):  
J M Duerden ◽  
G F Gibbons

Hepatic lipid synthesis was measured in rats in vivo with 3H2O, and the appearance of label in triacylglycerol and its constituent fatty acid and glycerol moieties was determined. In rats treated with Triton WR1339, the amount of newly synthesized fatty acid secreted as very-low-density lipoprotein (VLDL) triacylglycerol was greater during the dark phase of the diurnal cycle than during the light phase (11.3 versus 4.8 mumol of 3H2O/3 h per g of liver respectively). However, the total mass of VLDL triacylglycerol secreted remained constant, as did the amount of label in the secreted triacylglycerol glycerol. Newly synthesized fatty acids comprised only a small proportion of the total VLDL triacylglycerol fatty acids (TGFA) at both times (dark phase, 7.7%; light phase, 2.4%). Starvation for 24 h resulted in a small increase in the secretion of VLDL triacylglycerol. However, the contribution from newly synthesized fatty acids was decreased. Similar effects were observed in streptozotocin-diabetic animals. During the light and dark phases of the cycle, similar quantities of newly synthesized TGFA entered the hepatic cytosol, and these amounts were much smaller than those secreted as VLDL triacylglycerol. The mass of cytosolic triacylglycerol showed a diurnal variation, with a greater concentration during the light phase than in the dark. In diabetes, the mass of triacylglycerol was increased in the cytosol, as was the incorporation of labelled acylglycerol glycerol. Diabetes also abolished the diurnal variation in the quantity of cytosolic triacylglycerol. In each group of animals the specific radioactivity of the microsomal triacylglycerol was similar to that of the respective newly secreted plasma VLDL. The specific radioactivity of the cytosolic triacylglycerol was only 15.8% (dark phase) or 16.8% (light phase) that of the microsomal triacylglycerol. This increased to 35.5% in the starved animals and 40.2% in the diabetic animals.


1973 ◽  
Vol 132 (2) ◽  
pp. 329-340 ◽  
Author(s):  
Koyu Narumi ◽  
John M. Keller ◽  
Clinton E. Ballou

1. Mycobacterium phlei (A.T.C.C. 356) cells were incubated with 14C-labelled short-chain fatty acids and the 6-O-methylglucose-containing lipopolysaccharides that became esterified with radioactive acyl groups were isolated. The pattern of labelling of these lipopolysaccharides with the different acyl groups, the effects of different conditions on labelling patterns, and the kinetics of the turnover of 14C-labelled acyl groups were studied. 2. The labelling patterns are summarized as follows. [1-14C]Acetate was incorporated into all of the acyl groups. [1-14C]Propionate led to labelling of propionate and succinate, while [1-14C]isobutyrate was incorporated mostly as such, along with a trace amount in iso-octanoate. 3. Under the conditions of the experiments, [1-14C]acetate was rapidly incorporated into succinyl (3-carboxypropionyl) and octanoyl groups, whereas the acetyl groups themselves were labelled more slowly. Radioactivity in propionyl and succinyl groups, originating from [1-14C]propionate, attained maximum values and then gradually decreased in both. Incorporation of [1-14C]isobutyrate proceeded slowly but reached a plateau and remained constant. While n-butyrate is not a normal constituent of methyl-glucose-containing lipopolysaccharides, it was incorporated as such when n-[1-14C]-butyrate was supplied in the medium. 4. [1-14C]Acetyl groups were readily displaced by unlabelled acetate. On the other hand, the specific radioactivity of the succinyl group continued to increase during a 3h incubation with unlabelled succinate. Propionyl and succinyl groups, labelled by [1-14C]propionate, were displaced slowly by unlabelled propionate or succcinate. The isobutyryl group of the lipopolysaccharides did not turn over, in contrast to the results obtained with the other acyl substituents.


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