Interactions of insulin-like growth factor (IGF)-II and growth hormone in vivo: circulating levels of IGF-I and IGF-binding proteins in transgenic mice

1997 ◽  
pp. 701-708 ◽  
Author(s):  
A Blackburn ◽  
RA Dressendorfer ◽  
WF Blum ◽  
M Erhard ◽  
G Brem ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Transgene Expression ◽  
High Protein Diet ◽  
High Protein ◽  
Protein Diet ◽  
Standard Diet ◽  
Igf I ◽  
Igf Binding ◽  
B Mice

To study interactions between insulin-like growth factor-II (IGF-II) and growth hormone (GH) in vivo, we crossed hemizygous transgenic mice carrying phosphoenolpyruvate carboxykinase (PEPCK)-IGF-II fusion genes with hemizygous PEPCK-bovine GH (bGH) transgenic mice. Offspring harbouring both transgenes (IB), the IGF-II transgene (I) or the bGH transgene (B), and non-transgenic littermates (C) were obtained. Blood samples were taken before (end of week 12) and after (end of week 14) the mice had received a diet high in protein and low in carbohydrates to stimulate PEPCK promoter-controlled transgene expression. Mean serum GH concentrations of both B and IB mice corresponded to 900 ng/ml and increased more than twofold (P < 0.001) after 1 week of the high-protein diet. GH concentrations in controls and I mice were less than 20 ng/ml. Serum IGF-II concentrations in I and IB mice were three-to fourfold higher than those in C and B mice. Whereas IGF-II concentrations were not changed by the high-protein diet in the last two groups, serum IGF-II increased significantly in I (P < 0.001) and IB mice (P < 0.05). This increase was significantly (P < 0.05) less pronounced in IB than in C and I mice. Circulating IGF-I concentrations were about twofold (P < 0.001) higher in B and IB than in C and I mice, and showed a tendency to be lower in I than in C and in IB than in B mice when animals were maintained on the standard diet. The high-protein diet did not change circulating IGF-I concentrations in controls and B mice, but resulted in a significant reduction of serum IGF-I concentrations in I (P < 0.05) and IB mice (P < 0.001). Consequently, after PEPCK-IGF-II transgene expression was stimulated, serum IGF-I concentrations were significantly (P < 0.05) lower in I than in C and in IB than in B mice. Serum IGF-binding protein (IGFBP)-2 concentrations were significantly (P < 0.05) higher in I mice than in all other groups when mice were maintained on the standard diet, with a tendency to reduced IGFBP-2 concentrations in B mice. After the high-protein diet, serum IGFBP-2 concentrations did not change in C and I mice, but increased by two- to threefold in B and IB mice (P < 0.001). Serum IGFBP-3 concentrations tended to be greater in B and IB than in C and I mice, but these differences were mostly not significant. IGFBP-4 concentrations were significantly (P < 0.001) increased by GH overproduction in B and IB mice. Our data suggest that the reduction in circulating IGF-I concentrations by increased IGF-II is most probably due to the limited serum IGF binding capacity and the short half-life of free IGFs, rather than to a reduction in GH-dependent IGF-I production. Effects of GH overproduction on serum IGFBP-2 concentrations depend on dietary factors and may be both inhibitory and stimulatory.

scholarly journals Adaptive changes in the capacity of systems used for the synthesis of citrulline in rat liver mitochondria in response to high- and low-protein diets

1974 ◽  
Vol 142 (2) ◽  
pp. 359-364 ◽  
Author(s):  
J. D. McGivan ◽  
Norah M. Bradford ◽  
J. B. Chappell
Keyword(s):  
Nitrogen Source ◽  
High Protein Diet ◽  
Liver Mitochondria ◽  
High Protein ◽  
Protein Diet ◽  
Rat Liver Mitochondria ◽  
Standard Diet ◽  
Adaptive Changes ◽  
Low Protein ◽  
Citrulline Synthesis

1. Citrulline synthesis was measured in mitochondria from rats fed on a standard diet, a high-protein diet, or on glucose. 2. With NH4Cl as the nitrogen source the rate of citrulline synthesis was higher in mitochondria from rats fed on a high-protein diet than in those from rats fed on a standard diet. When rats were fed solely on glucose the rate of synthesis of citrulline from NH4Cl was very low. 3. With glutamate as the nitrogen source the relative rates of citrulline synthesis were much lower than when NH4Cl was present, but similar adaptive changes occurred. 4. The activity of the mitochondrial glutamate-transporting system increased two to three times on feeding rats on a high-protein diet, but the Km for glutamate was unchanged. 5. Adaptive changes in certain intramitochondrial enzymes were also measured. 6. The results were interpreted to indicate that when an excess of substrate was present, citrulline synthesis from NH4Cl was rate-limited by the intramitochondrial concentration of N-acetyl-glutamate, but citrulline synthesis from glutamate was rate-limited primarily by the activity of the glutamate-transporting system.

Glomerular size selectivity in nephrotic rats exposed to diets with different protein content

1987 ◽  
Vol 253 (2) ◽  
pp. F318-F327
Author(s):  
A. Remuzzi ◽  
C. Battaglia ◽  
L. Rossi ◽  
C. Zoja ◽  
G. Remuzzi
Keyword(s):  
High Protein Diet ◽  
Urinary Protein Excretion ◽  
Urinary Protein ◽  
High Protein ◽  
Protein Diet ◽  
Standard Diet ◽  
Size Selectivity ◽  
Protein Excretion ◽  
Fractional Clearance ◽  
Glomerular Size

Glomerular size-selective properties in animals made nephrotic by adriamycin (ADR) injection and fed standard (20% protein) or high-protein (35% protein) diets were investigated using dextran fractional clearances. To interpret filtration and dextran-sieving data, a theoretical approach previously developed for analysis of experimental data in healthy and nephrotic humans was used. Four types of hypothetical pore-radius distributions were compared in order to establish the best tool for describing membrane pore structure in normal and nephrotic rats. This analysis revealed that a spread distribution of pores, the lognormal probability distribution, is the most adequate in representing membrane intrinsic characteristics. ADR animals on standard diet developed massive proteinuria and a lower glomerular filtration rate (GFR) than control animals. High-protein feeding in ADR rats induced a further increase in urinary protein excretion and in GFR. Dextran fractional clearance was more elevated for larger dextran fractions (greater than 46 A) in ADR animals on the standard diet than in control rats. No differences were observed in dextran-sieving curves between ADR rats on the standard and high-protein diet. Theoretical analysis of filtration and fractional clearance data revealed comparable changes in the intrinsic parameters of glomerular size selectivity in the two groups of nephrotic animals. These observations indicate that increased traffic of plasma proteins through the glomerular capillary wall does not imply, in our experimental condition, a further loss of glomerular size-selective properties. The greater urinary protein excretion of ADR animals on high-protein diet than ADR animals on a standard diet cannot be explained by further impairment of glomerular size selectivity but more likely reflects hemodynamic changes.

scholarly journals High Protein Diet Induces Oxidative Stress in Rat Cerebral Cortex and Hypothalamus

2019 ◽  
Vol 20 (7) ◽  
pp. 1547 ◽  
Author(s):  
Ewa Żebrowska ◽  
Mateusz Maciejczyk ◽  
Małgorzata Żendzian-Piotrowska ◽  
Anna Zalewska ◽  
Adrian Chabowski
Keyword(s):  
Oxidative Stress ◽  
Cerebral Cortex ◽  
Oxidative Damage ◽  
Antioxidant Defense ◽  
High Protein Diet ◽  
Brain Structures ◽  
High Protein ◽  
Protein Diet ◽  
Standard Diet ◽  
The Impact

This is the first study to analyze the impact of high protein diet (HPD) on antioxidant defense, redox status, as well as oxidative damage on both a local and systemic level. Male Wistar rats were divided into two equal groups (n = 9): HPD (44% protein) and standard diet (CON; 24.2% protein). After eight weeks, glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), superoxide dismutase-1 (SOD-1), reduced glutathione (GSH), uric acid (UA), total antioxidant (TAC)/oxidant status (TOS) as well as advanced glycation end products (AGE), 4-hydroxynonenal (4-HNE), and malondialdehyde (MDA) were analyzed in the serum/plasma, cerebral cortex, and hypothalamus of HPD and CON rats. HPD resulted in higher UA concentration and activity of GPx and CAT in the hypothalamus, whereas in the cerebral cortex these parameters remained unchanged. A significantly lower GSH content was demonstrated in the plasma and hypothalamus of HPD rats when compared to CON rats. Both brain structures expressed higher content of 4-HNE and MDA, whereas AGE was increased only in the hypothalamus of HPD animals. Despite the enhancement in antioxidant defense in the hypothalamus, this mechanism does not protect the hypothalamus from oxidative damage in rats. Hypothalamus is more susceptible to oxidative stress caused by HPD.

scholarly journals 136HIGH PROTEIN DIET INHIBITS INNER CELL MASS FORMATION AND INCREASES APOPTOSIS IN MOUSE BLASTOCYSTS DEVELOPED IN VIVO BY INCREASING THE LEVELS OF AMMONIUM IN THE REPRODUCTIVE TRACT

2004 ◽  
Vol 16 (2) ◽  
pp. 190 ◽  
Author(s):  
D.K. Gardner ◽  
K.S. Stilley ◽  
M. Lane
Keyword(s):  
Reproductive Tract ◽  
Cell Mass ◽  
High Protein Diet ◽  
Female Reproductive Tract ◽  
High Protein ◽  
Protein Diet ◽  
Control Group ◽  
Oviduct Fluid ◽  
Mass Formation

Ammonium is known to adversely affect the development of mouse embryos in culture. Specifically, ammonium has been found to impair inner cell (ICM) mass formation, increase apoptosis, retard fetal development following embryo transfer and induce exencephaly. Significantly, high protein diets in cattle lead to reduced fecundity. This has been linked to elevated urea levels within fluid of the female tract. In this study we have determined the effects of a high protein diet for mice on the levels of ammonium within the female tract and the effects of such a diet on the development and viability of blastocysts developed in vivo. Outbred mice (CF1) were fed a diet of either 25% (high protein) or 14% (control) protein for 4 weeks. Females were superovulated and mated to males of the same strain. In 24 mice, oviduct fluid was collected at 22h post hCG. Ammonium in the oviduct fluid was then quantitated fluorometrically. From other animals, blastocysts were flushed 92h post hCG and analyzed. Blastocyst differentiation and apoptotic indices were determined. Values are mean±SEM. Data were analysed using Student’s t-test. The levels of ammonium in the oviduct were significantly higher (P&lt;0.01) in females fed the high protein diet (356±43μM) compared to the control (68±13μM) (n=12 in each group). Blastocysts (n=139) from females fed the high protein diet had significantly lower total (43.4±1.1; P&lt;0.05) and ICM cell numbers (12.7±0.4; P&lt;0.01), compared to the control group (46.8±0.9 and 15.4±0.4 respectively; n=124). Furthermore, blastocysts from animals fed a high protein diet had a significantly higher apoptotic index (8.7±1.4; P&lt;0.01) compared to the control group (2.0±0.5). These data show that consumption of a high protein diet results in the excess accumulation of ammonium in the fluid of the female reproductive tract of mice. These high levels of ammonium subsequently impair the formation of the fetal progenitor cells and increase cell death at the blastocyst stage. These data from in vivo-developed mouse blastocysts are similar to those for blastocysts developed in culture in the presence of 300μM ammonium. Therefore, it is not advisable to maintain mice on a high protein diet. These data have significant implications for animal breeding, and for patients attempting IVF treatment.

Splanchnic sequestration of amino acids in aged rats: in vivo and ex vivo experiments using a model of isolated perfused liver

2008 ◽  
Vol 294 (3) ◽  
pp. R748-R755 ◽  
Author(s):  
M. Jourdan ◽  
L. Cynober ◽  
C. Moinard ◽  
M. C. Blanc ◽  
N. Neveux ◽  
...  
Keyword(s):  
Amino Acids ◽  
Ex Vivo ◽  
High Protein Diet ◽  
High Protein ◽  
Protein Diet ◽  
Aged Rats ◽  
Sprague Dawley ◽  
Adult Rats ◽  
Urea Production

Splanchnic sequestration of amino acids (SSAA) is a process observed during aging that leads to decreased peripheral amino acid (AA) availability. The mechanisms underlying SSAA remain unknown. The aim of the present study was to determine whether a high-protein diet could increase nitrogen retention in aged rats by saturating SSAA and whether SSAA could be explained by dysregulation of hepatic nitrogen metabolism. Adult and aged male Sprague-Dawley rats were housed in individual metabolic cages and fed a normal-protein (17% protein) or high-protein diet (27%) for 2 wk. Nitrogen balance (NB) was calculated daily. On day 14, livers were isolated and perfused for 90 min to study AA and urea fluxes. NB was lower in aged rats fed a normal-protein diet than in adults, but a high-protein diet restored NB to adult levels. Isolated perfused livers from aged rats showed decreased urea production and arginine uptake, together with a release of alanine (vs. uptake in adult rats) and a hepatic accumulation of alanine. The in vivo data suggest that SSAA is a saturable process that responds to an increase in dietary protein content. The hepatic metabolism of AA in aged rats is greatly modified, and urea production decreases. This result refutes the hypothesis that SSAA is associated with an increase in AA disposal via urea production.

Corrigendum to: IGF-I is not a useful marker for nutritional status in the growing pig under commercial conditions

2001 ◽  
Vol 52 (7) ◽  
pp. 791
Author(s):  
L. Ma ◽  
F. R. Dunshea ◽  
Y. M. Brockwell ◽  
R. L. Inglis ◽  
D. J. Kingston ◽  
...  
Keyword(s):  
Weight Gain ◽  
Nutritional Status ◽  
Dietary Protein ◽  
High Protein Diet ◽  
High Protein ◽  
Protein Diet ◽  
Low Protein ◽  
Igf I ◽  
Protein Diets

Plasma hormone concentrations were measured in gilts after fasting, long-term protein restriction, or supplementation. In 11-week-old pigs fasted overnight, plasma insulin, glucagon, gastrin, urea, and glucose were increased 30 min after re-feeding (P < 0.05), whereas IGF-I did not change. In 16-week-old gilts fed a standard commercial diet [14.6% crude protein (CP)], or a high-protein diet (16.7% CP) for 4 weeks, the high-protein diet increased weight gain (13%; P < 0.05) and carcass weight (4%; P < 0.05), but did not alter plasma IGF-I, insulin, or glucagon. In 10-week-old gilts fed high-protein diets (19.4% and 18.3% CP), or low-protein diets (15.5% and 13.3% CP) for 12 weeks during the grower and finisher phases, respectively, the low-protein diet decreased weight gain (18%; P < 0.001) and carcass weight (11%; P < 0.01), with a marked increase in plasma glucagon (P < 0.05), no change in insulin, and only a trend towards decreased IGF-I (P = 0.1). The pigs were more sensitive to altered dietary protein at 10 weeks of age than at 16 weeks. Plasma IGF-I was not responsive to the short-term effects of feeding or the long-term effects of dietary protein. Glucagon could provide a useful marker for nutritional status in young pigs, provided that time of feeding is taken into account.

Fluxes and membrane transport of amino acids in rat liver under different protein diets

1990 ◽  
Vol 259 (5) ◽  
pp. E614-E625 ◽  
Author(s):  
P. Fafournoux ◽  
C. Remesy ◽  
C. Demigne
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Aromatic Amino Acids ◽  
High Protein Diet ◽  
High Protein ◽  
Protein Diet ◽  
Transport Systems ◽  
Low Concentrations ◽  
Significant Uptake

The aim of the present work was to evaluate in vivo the role of the transport step in hepatic amino acid metabolism. To vary hepatic utilization of amino acids, rats were adapted to diets containing various concentrations of casein (5, 15, and 60%). In rats fed 5 or 15% casein diets, Gln and Glu were released by the liver, and there was a significant uptake of Ala. Hepatic fluxes of amino acids increased considerably after adaptation to high-casein diet (up to 1.55 mumol.min-1.g liver-1 for Ala), because of the rise in afferent concentrations as well as enhanced uptake percentage (peaking at 60–75% for most glucogenic amino acids). Adaptation to a high-protein diet led to induction of not only system A but also of most of the other transport systems (Gly, anionic, T, y+, and to a lesser extent system N); only systems ASC and L were unchanged. The study of amino acid repartition between liver and plasma with different diets indicates that transport could modulate utilization of Ala, Ser, Thr, Gly, Gln, and Asp. For Arg and Asn, present in very low concentrations in liver under any condition, the transport step should be the major locus of control of their metabolism. For amino acids chiefly transported by nonconcentrative systems, such as aromatic amino acids, cellular metabolism could also be limited by the transport process. In conclusion, during adaptation to a high-protein diet, there is apparently a coordinated adaptation of amino acid transport and of their intracellular metabolism. For some amino acids, induction of catabolic enzymes seems greater than that of transport, so that the transport step may play an important role in control of metabolic fluxes. For example, concentration of amino acids such as Thr may be markedly depressed in rats adapted to a high-protein diet.

scholarly journals Effects of a High-Protein Diet on in vivo Fatty Acid Synthesis and the Activities of Lipogenic Enzymes in Liver of Chicks

1979 ◽  
Vol 50 (8) ◽  
pp. 582-591
Author(s):  
Toshio MIZUNO ◽  
Koji AMANO ◽  
Keizo ONO ◽  
Yuzo HIKAMI ◽  
Shin HASEGAWA
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
High Protein Diet ◽  
Acid Synthesis ◽  
High Protein ◽  
Protein Diet ◽  
Lipogenic Enzymes

IGF-I is not a useful marker for nutritional status in the growing pig under commercial conditions

2001 ◽  
Vol 52 (5) ◽  
pp. 603
Author(s):  
L. Ma ◽  
F. R. Dunshea ◽  
Y. M. Brockwell ◽  
R. L. Inglis ◽  
D. J. Kingston ◽  
...  
Keyword(s):  
Weight Gain ◽  
Nutritional Status ◽  
Dietary Protein ◽  
High Protein Diet ◽  
High Protein ◽  
Protein Diet ◽  
Low Protein ◽  
Igf I ◽  
Protein Diets

Plasma hormone concentrations were measured in gilts after fasting, long-term protein restriction, or supplementation. In 11-week-old pigs fasted overnight, plasma insulin, glucagon, gastrin, urea, and glucose were increased 30 min after re-feeding (P < 0.05), whereas IGF-I did not change. In 16-week-old gilts fed a standard commercial diet [14.6% crude protein (CP)], or a high-protein diet (16.7% CP) for 4 weeks, the high-protein diet increased weight gain (13%; P < 0.05) and carcass weight (4%; P < 0.05), but did not alter plasma IGF-I, insulin, or glucagon. In 10-week-old gilts fed high-protein diets (19.4% and 18.3% CP), or low-protein diets (15.5% and 13.3% CP) for 12 weeks during the grower and finisher phases, respectively, the low-protein diet decreased weight gain (18%; P < 0.001) and carcass weight (11%; P < 0.01), with a marked increase in plasma glucagon (P < 0.05), no change in insulin, and only a trend towards decreased IGF-I (P = 0.1). The pigs were more sensitive to altered dietary protein at 10 weeks of age than at 16 weeks. Plasma IGF-I was not responsive to the short-term effects of feeding or the long-term effects of dietary protein. Glucagon could provide a useful marker for nutritional status in young pigs, provided that time of feeding is taken into account.

High Protein Diet and Phenylalanine Hydroxylase Activities in Rats

Pteridines ◽  
1989 ◽  
Vol 1 (4) ◽  
pp. 235-238 ◽  
Author(s):  
Michael P. Carty ◽  
Edel Beirne ◽  
John Donlon
Keyword(s):  
Rat Liver ◽  
Phenylalanine Hydroxylase ◽  
High Protein Diet ◽  
High Protein ◽  
Protein Diet ◽  
Casein Diet ◽  
Dependent Activity ◽  
Liver And Kidney ◽  
Phenylalanine Metabolism

SummaryThe effects of a diet of 85% casein on the activities of the phenylalanine hydroxylases of rat liver and kidney have been compared. Whereas only the tetrahydrobiopterin-dependent activity of rat hepatic phenylalanine hydroxylase is significantly stimulated, both the tetrahydrobiopterin-dependent and the dimethyltetrahydropterin- dependent activities of the renal enzyme are significantly decreased, after five days of feeding a casein diet. The animals fed a high protein diet for seven days have an increased rate of phenylalanine catabolism in vivo, which is also reflected in increased flux of label from phenylalanine into glucose. The regulation of phenylalanine metabolism, under these conditions, is discussed.

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