Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0038187 (starvation)
24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Well-fed castrated male sheep (N = 3) and 125 days gestation pregnant ewes (N = 6) with chronically catheterized fetuses were fasted for 72 h. Insulin-like growth factor-binding protein (IGFBP) levels in fed and starved fetal, maternal and castrated male sheep plasma were measured using ligand blot analysis. IGFBPs in adult and fetal sheep differed in distribution both before and after 72 h starvation. IGFBP-3 was the major postnatal binding protein, while in the fetus IGFBP-2, IGFBP-3 and the circulating IGF type 2 receptor fragment each contributed 25-30% of total IGF binding capacity. After starvation, total IGF binding capacity and IGFBP-3 fell in plasma of maternal and castrated male sheep (p less than 0.05). Total IGF binding capacity rose with starvation in fetal plasma (p less than 0.05) as a result of an increase in IGFBP-1 (p less than 0.01) and IGFBP-2 (p less than 0.05). The different nutritional control of the IGFBPs in the fetus and the adult may reflect ontogenic differences in the regulation and function of circulating IGFs and their binding proteins.
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PMID:Ontogenic differences in the nutritional regulation of circulating IGF binding proteins in sheep plasma. 137 Oct 31

We have reported previously that levels of insulin-like growth factor I (IGF-I) and IGF-II in fetal sheep plasma decrease with maternal starvation and increase following an infusion of glucose to the starved fetus, while a fetal infusion of insulin elevates UGF-I alone. We now report the changes in the circulating IGF-II/M6P receptor and plasma IGF binding proteins (IGFBPs), as measured by western blotting and ligand blotting, respectively, in fetus and mother during this study. In fetal plasma, the circulating IGF-II/mannose-6-phosphate (M6P) receptor, IGFBP-3 and IGFBP-4 were reduced during starvation. While circulating IGF-II/M6P receptor and IGFBP-4 levels were increased following the fetal insulin or glucose infusion, IGFBP-3 was unchanged and increased only after 48 h of maternal refeeding. Both IGFBP-1 and IGFBP-2 increased with starvation but while IGFBP-1 levels returned to control values following both insulin and glucose infusion, levels of IGFBP-2 were not reduced significantly by either infusion or by refeeding. In maternal plasma, levels of IGFBP-3 and IGFBP-4 decreased while IGFBP-1 and IGFBP-2 increased after 48 h of starvation. Levels of each IGFBP were unaltered following the fetal infusions but returned to values obtained during the control period after refeeding. These data show that each of the IGF carrier proteins is sensitive of changes in nutrition, either acutely, such as IGFBP-1, or chronically, as for IGFBP-3. This suggests that the circulating IGF-II/M6P receptor and the IGFBP's may modulate IGF activity in the fetus during different nutritional states.
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PMID:Circulating insulin-like growth factor II/mannose-6-phosphate receptor and insulin-like growth factor binding proteins in fetal sheep plasma are regulated by glucose and insulin. 752 43

Maternal malnutrition adversely affects fetal body and brain growth during late gestation. We utilized a fetal brain cell culture model to examine whether alternations in circulating factors may contribute to reduce brain growth during maternal starvation; we then used specific immunoassay and western blotting techniques, and purified peptides to investigate the potential role that altered levels of insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs) may play in impaired growth during maternal nutritional restriction. Fetal, body, liver, and brain weight were reduced after 72 hr maternal starvation, and plasma from starved fetuses were less potent than fed fetal plasma in stimulating brain cell growth. Circulating levels of IGF-I were reduced in starved compared to fed fetuses, while levels of IGF-II were similar in both groups. In contrast, [125I]-IGF-I binding assay demonstrated an increase in the availability of plasma IGFBPs following starvation. Western ligand blotting and densitometry indicated that levels of 32 Kd IGFBPs were 2-fold higher in starved compared to fed fetal plasma. Immunoblotting and immunoprecipitation with antiserum against rat IGFBP-1 confirmed that heightened levels of immunoreactive IGFBP-1 accounted for the increase in 32 Kd IGFBPs in starved plasma. Levels of 34 Kd BPs, representing IGFBP-2, were unaffected by starvation. Reconstitution experiments in cell culture showed that IGF-I promoted fetal brain cell growth, and that when they were supplemented with IGF-I, the growth promoting activity of starved fetal plasma was restored to fed levels. These changes were measured using MTT to assess mitochondrial reductase activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Insulin-like growth factors and binding proteins in the fetal rat: alterations during maternal starvation and effects in fetal brain cell culture. 851 Jul 96

This study has evaluated the effects of recombinant human insulin-like growth factor I (rhIGF-I) to moderately stressed post-operative patients provided with dextrose as the only exogeneous substrate. Thirty patients who underwent elective colorectal surgery were randomized to receive either rhIGF-I (80 micrograms kg-1 bw) subcutaneously twice daily or placebo injections in a double-blind parallel group design. Nitrogen balance, urinary 3-methyl-histidine excretion plasma growth hormone (GH), serum cortisol, IGF-I binding proteins (IGFBP-1,3), glomerular filtration rate, plasma amino acid concentrations and whole-body energy expenditures were measured as effector variables during days 1-5 post-operatively. Animal and isolated tissue experiments were performed as additional control experiments to confirm cellular effectiveness of the recombinant material. rhIGF-I increased significantly the glomerular filtration rate and prevented the adaptive decrease in whole-body energy expenditure in response to partial starvation in the postoperative period. Serum and plasma concentrations of IGFBP-1,3 cortisol, blood glucose and amino acids were not significantly influenced by rhIGF-I administration, while plasma GH levels decreased significantly as expected. rhIGF-I had no effect on either nitrogen balance or protein breakdown (3-methylhistidine excretion) in post-operative patients on dextrose supplementation only, although plasma concentrations of IGF-I increased from 130-140 ng mL-1 to a range of 300-450 ng mL-1. In contrast, IGF-I stimulated the synthesis of both globular and myofibrillar proteins (+50%, P < 0.01), when given as a single dose (100 micrograms kg-1) 2 h before measurements of protein synthesis in skeletal muscles of overnight fasted adult mice. This stimulatory effect by IGF-I (1 microgram mL-1) was also confirmed by measurements of skeletal muscle protein synthesis in vitro (+40%, P < 0.05). Orally re-fed mice had a normal transcription of IGF-I mRNA in skeletal muscle cells, while overnight fasted mice showed a trend to down-regulated transcription. Our results demonstrate that rhIGF-I has several significant physiological effects, without major side-effects, when supplied to partially starved patients in the post-operative phase. The lack of a whole-body nitrogen sparing effect by rhIGF-I alone to post-operative patients is not clear, but was most likely explained by subnormal plasma concentrations of amino acids.
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PMID:The effect of recombinant human IGF-I on protein metabolism in post-operative patients without nutrition compared to effects in experimental animals. 855 66

We have investigated the expression and secretion of insulin-like growth factor binding proteins (IGFBPs-1 to -6) in human vascular smooth muscle cells (hVSMCs) cultured from human renal arteries. Solution hybridization was used to determine IGFBP mRNA levels and Western immunoblot to detect the corresponding peptides. The hVSMCs expressed mRNAs for IGFBPs-2 to -6; IGFBP-1 mRNA was not detected. IGFBPs-3, -4 and -6 mRNAs were the most abundant, IGFBP-5 was also highly expressed, whereas the IGFBP-2 mRNA was just above the limit of detection. Serum starvation for 48 h significantly decreased the mRNA levels of IGFBPs-2 to -5 and tended to decrease IGFBP-6 mRNA also. IGFBPs-2, -4, -5 and -6 peptides could be detected in conditioned medium, but IGFBP-3 peptide was not detected. IGFBP-4 was the only peptide detected without any concentration step. Low-molecular-mass immunoreactive degradation products were found for IGFBPs-2 and -4. Exogenous IGFBPs-1, -3 and -4 in concentrations of 50 ng/ml inhibited DNA synthesis induced by 1 nM IGF-I, whereas IGFBPs-2, -5 and -6 had no significant inhibitory effects at this concentration. We conclude from these results that all IGFBPs except IGFBP-1 are expressed in hVSMC. Our results indicate that locally produced, in addition to circulating, IGFBPs may have an important role in the regulation of hVSMC.
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PMID:Insulin-like growth factor binding proteins-2 to -6 are expressed by human vascular smooth muscle cells. 1055 78

The golden-mantled ground squirrel, Spermophilus lateralis, undergoes a profound winter hibernation that represents, among other changes, a prolonged period of starvation. In addition to dramatic metabolic and other physiological adaptations during hibernation which serve to reduce fuel energy expenditure, we have hypothesized that there may also be significant changes in the endocrine axis that regulates energetically-expensive somatic growth. As compared with euthermic, non-hibernating controls, hibernating S. lateralis were found to have 75%-reduced serum concentrations of insulin-like growth factor-I (IGF-I; from approximately 625 to approximately 150 ng/ml in both females and males, P < 0.05). While IGFBP-3 was the predominant IGFBP in serum of the euthermic controls, its levels were reduced to a similar degree in serum from the hibernating animals. IGFBP-4 was present at relatively low levels in the euthermic controls, and was reduced to undetectable levels in hibernating animals. Surprisingly, there was no IGFBP detectable in the 30 kDa range in either euthermic or hibernating S. lateralis, suggesting that IGFBP-1 does not play a role in hibernation-related changes in the IGF axis. In accordance with these endocrine changes, when serum from hibernating S. lateralis was added to cartilage explant cultures (at a 5% v/v concentration), it exhibited no ability to alter (35)S-proteoglycan synthetic rate, whereas serum from the euthermic squirrels significantly stimulated synthetic activity by 2-fold. These results suggest that part of hibernation adaptation in S. lateralis includes down-regulation in the growth-regulatory IGF axis. J. Exp. Zool. 289:66-73, 2001.
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PMID:Down-regulation in the insulin-like growth factor (IGF) axis during hibernation in the golden-mantled ground squirrel, Spermophilus lateralis: IGF-I and the IGF-binding proteins (IGFBPs). 1116 94

Regulation of gene expression by nutrients in mammals is an important mechanism allowing them to adapt their physiological functions according to the supply of nutrient in the diet. It has been shown recently that amino acids are able to regulate by themselves the expression of numerous genes. CHOP, asparagine synthetase, and IGFBP-1 regulation following AA starvation will be described in this review with special interest in the molecular mechanisms involved.
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PMID:Amino acids as regulators of gene expression: molecular mechanisms. 1468 83

The insulin-like growth factor axis is highly responsive to nutritional status and may be involved as one of the underlying mechanisms through which caloric restriction could affect cancer risk. High levels of circulating insulin-like growth factor (IGF)-I, or IGF-I relative to IGF binding protein (IGFBP)-3 have been related to various human cancer types. In a group of 87 postmenopausal women, we found that childhood exposure to the 1944-1945 Dutch famine was associated with increased plasma levels of IGF-I and IGFBP-3, whereas IGFBP-1 and -2 levels were weakly decreased. These results are opposite to immediate responses seen under starvation and we hypothesize that this could indicate a permanent overshoot upon improvement of nutritional status after the famine.
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PMID:Long term consequences of the 1944-1945 Dutch famine on the insulin-like growth factor axis. 1469 31

A dramatic overexpression of IGFBP-1 is responsible for growth inhibition, in response to a low-protein diet feeding. It has been demonstrated that a fall in the amino acid concentration was directly responsible for IGFBP-1 induction. In this report, we sought to determine the mechanism by which amino acid limitation upregulates IGFBP-1 expression. Our results show that both transcriptional activation and mRNA stabilization are involved. We also demonstrate that (i) the mGCN2/ATF4 pathway is not involved in this regulation and (ii) the 3'UTR of IGFBP-1 mRNA is responsible for its destabilization and regulates its stability in response to amino acid starvation.
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PMID:Induction of IGFBP-1 expression by amino acid deprivation of HepG2 human hepatoma cells involves both a transcriptional activation and an mRNA stabilization due to its 3'UTR. 1586 98

The insulin-like growth factor (IGF) signaling pathway is a conserved pathway that regulates animal development, growth, metabolism, reproduction, and aging. The biological actions of IGFs are modulated by IGF-binding proteins (IGFBPs). Although the structure and function of fish IGFBP-1, -2, -3, and -5 have been elucidated, there is currently no report on the full-length structure of a fish IGFBP-4 nor its biological action. In this study, we cloned and characterized the IGFBP-4 gene from fugu. Sequence comparison, phylogenetic, and synteny analyses indicate that its chromosomal location, gene, and protein structure are similar to its mammalian orthologs. Fugu IGFBP-4 mRNA was easily detectable in all adult tissues examined with the exception of spleen. Older animals tended to have higher levels of IGFBP-4 mRNA in the muscle and eyes compared with younger animals. Starvation resulted in significant increases in IGFBP-4 mRNA abundance in the muscle, liver, gallbladder, and brain. Overexpression of fugu and human IGFBP-4 in zebrafish embryos caused a significant decrease in body size and somite number, suggesting that fugu IGFBP-4 inhibits growth and development, possibly by binding to IGFs and inhibiting their binding to the IGF receptors. These results provide new information about the structural and functional conservation, expression patterns, and physiological regulation of the IGFBP-4 gene in a teleost fish.
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PMID:Structural, gene expression, and functional analysis of the fugu (Takifugu rubripes) insulin-like growth factor binding protein-4 gene. 1909 10


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