Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
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 studied the role of the mitochondrial 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) synthase gene in regulating ketogenesis. The gene exhibits expression in various tissues and it is regulated in a tissue-specific manner. To investigate the underlying mechanisms of this expression, we linked a 1148-base-pair portion of the mitochondrial HMG-CoA synthase promoter to the human growth hormone (hGH) gene and analyzed the expression of the hGH reporter gene in transgenic mice. mRNA levels of hGH were observed in liver, testis, ovary, stomach, colon, cecum, brown adipose tissue, spleen, adrenal glands, and mammary glands from adult mice, and also in liver and stomach, duodenum, jejunum, brown adipose tissue, and heart of suckling mice. There was no expression either in kidney or in any other nonketogenic tissue. The comparison between these data and those of the endogenous mitochondrial HMG-CoA synthase gene suggests that the 1148 base pairs of the promoter contain the elements necessary for expression in liver and testis, but an enhancer is necessary for full expression in intestine of suckling animals and that a silencer prevents expression in stomach, brown adipose tissue, spleen, adrenal glands, and mammary glands in wild type adult mice. In starvation, transgenic mice showed higher expression in liver than did wild type. Both refeeding and insulin injection reduced the expression. Fat diets, composed in each case of different fatty acids, produced similar expression levels, respectively, to those found in wild type animals, suggesting that long-, medium-, and short-chain fatty acids may exert a positive influence on the transcription rate in this 1148-base-pair portion of the promoter. The ketogenic capacity of liver and the blood ketone body levels were equal in transgenic mice and in nontransgenic mice.
 ...
PMID:Tissue-specific expression and dietary regulation of chimeric mitochondrial 3-hydroxy-3-methylglutaryl coenzyme A synthase/human growth hormone gene in transgenic mice. 863 84

"Septic autocannabalism" been coined to describe the metabolic response that follows severe sepsis in humans. The normal protein- and energy-conserving mechanisms evoked during simple starvation are not observed following the onset of sepsis. The metabolic response to sepsis entails rapid breakdown of the body's reserves of protein, carbohydrate, and fat. Hyperglycemia with insulin resistance, profound negative nitrogen balance, and diversion of protein from skeletal muscle to splanchnic tissues are prominent features. These responses are believed to be mediated in large part by inflammatory cytokines such as tumor necrosis factor alpha (TNFalpha), interleukin 1beta (IL-1beta), and IL-6. Secondary induction of catecholamines, cortisol, and glucagon by cytokines is likely to be another important effector mechanism. Infection and inflammation elicit a complex network of interwoven responses, and no single mediator alone accounts for the responses observed. Sepsis also commonly involves alterations in cardiovascular function with altered flow to key metabolic sites, hypoxia, damage to the gut's mucosal barrier, secondary organ failure, and alterations in capillary permeability. These structural and functional alterations also strongly influence the metabolic profile during infection. If these catabolic responses persist for more than a few days, severe malnutrition results and is likely to be an important risk factor for mortality in these patients. The altered metabolic milieu during sepsis prevents effective use of exogeneously delivered glucose and protein; at best, administration of these agents ameliorates but does not prevent the persistence of catabolism. Delivery of agents that antagonize cytokines and other moieties such as glutamine and growth hormone may, in the future, help to restore nitrogen balance during sepsis.
 ...
PMID:Metabolism of sepsis and multiple organ failure. 866 35

A specific and sensitive homologous radioimmunoassay for eel (Anguilla anguilla L.) growth hormone (angGH) has been developed. The antiserum, raised against purified angGH and used at 1:20,000 final dilution, did not cross-react with eel prolactin or thyrotropin, carp gonadotropin II, bovine GH, or serum from hypophysectornized eel. The inhibition curves for eel pituitary extracts and serum were parallel to that of angGH standard. The ED50 value was between 1 and 2 ng/tube and the recovery of purified angGH added to the serum was about 100%. In immunocytochemical studies, the antiserum, used at 1:1000 dilution, specifically labeled the somatotrophs in the pituitaries of the glass, yellow, and silver eels. The GH contents were determined in the pituitaries of glass, yellow, and silver eels and in the serum at the yellow and silver stages. GH variations during the transformation of the yellow to silver eel were examined. The results indicated a decrease in GH production between the yellow and the silver eels, possibly related to the cessation of growth at the silver stage. In contrast to the situation in the naturally fasting silver eel, submitting yellow eels to 3 months of starvation (experimental fasting) greatly increased GH production. This suggests a variation in the regulation of GH according to the type of fasting (natural or experimental) and/or the stage of the fish (yellow or silver).
 ...
PMID:Development of a radioimmunoassay for European eel growth hormone and application to the study of silvering and experimental fasting. 880 66

We examined in a factorial design the effect of dietary protein (45%, 52% and 60%) and lipids (8%, 12%, 17%) on growth performance and circulating growth hormone (GH) levels of fingerling sea bream (5-month-old) fed to satiation with self-feeders. Daily weight gain (2.6-2.9%) and feed gain ratio (1.1-1.3) of fish fed high protein-low lipid diets were comparable to those found in fast growing strains of rainbow trout. However, increasing hyperphagia in association with the decrease of daily weight gain and feed conversion efficiency were found with the decrease of dietary protein:energy ratio. This growth impairment was linked to increased concentrations of circulating GH, which would exacerbate glucose and lipid intolerance. We consider the elevated concentration of circulating GH to be a risk factor leading to some state of metabolic starvation, in which feeding behavior and feed conversion efficiency are largely altered. From our results, it can be also concluded that circulating and pituitary GH availability decreases progressively from 1- to 3-year-old fish. This blunted GH synthesis and release is discussed in relation to age decrease in the optimum dietary protein:energy ratio.
 ...
PMID:Growth hormone as a function of age and dietary protein: energy ratio in a marine teleost, the gilthead sea bream (Sparus aurata). 897 55

Anorexia nervosa is associated with multiple endocrine abnormalities. Hypothalamic neuropeptides and monoamines are involved in the regulation of human appetite, and they are changed in several ways in anorexia nervosa. But it remains to be clarified whether these alterations are secondary or etiologic. Feeding behaviour in anorexia nervosa is characterised by a strong ambivalence and not by loss of appetite. Hypothalamic amenorrhea is a diagnostic criterion, and is not only secondary as it often precedes the weight loss and persists for a long time after weight and motor activity have returned to normal. Hypersecretion of corticotropin releasing hormone seems to be secondary to starvation, but at the same time it may keep up and intensify the anorexia, physical hyperactivity and amenorrhea. Low production of insulinlike growth factor-I and high growth hormone secretion reflects the nutritional deprivation. In conclusion most of the neuroendocrine abnormalities are secondary to weight loss, but some of them seem to participate in a circulus vitiosus and maintain the emaciated state.
 ...
PMID:[Neuroendocrine disorders in anorexia nervosa--primary or secondary?]. 899 10

The case of a woman of 27 affected by the Prader-Willi syndrome who underwent general anaesthesia for dental surgery is reported. The patient presented severe mental retardation, small stature, moderate muscular hypotonia, hyperphagia, obesity, and diabetes mellitus. Premedication consisted of diazepam and atropine; anaesthesia was induced with propofol and maintained with propofol, fentanyl and N2O; muscle paralysis was obtained with atracurium. A small glottis was observed at laryngoscopy so that a 6 mm cuffed tube was inserted. Surgery lasted 75 minutes; the patient recovered promptly a few minutes following the end of propofol infusion; no postoperative complication was recorded. As hypoglycemia can occur during and after surgery in the Prader-Willi syndrome, plasma samples for glucose, NEFA, insulin, cortisol, and growth hormone (GH) were collected prior to the induction of anaesthesia (A), 20 minutes after starting surgery (B), at the end of surgery (C), and 3 hours later (D). In spite of the infusion of glucose, hyperglycemia was observed just in C and D samples (A:77; B:88; C:245; D:279 mg/dl). Stable NEFA values, within the normal range, were observed (A:77; B:88; C:245; D:279 mg/dl) suggesting poor or absent lipolysis. Insulin decreased progressively during surgery (A:10.5; B:8.8; C:5.4; D:7.0 mU/L). Cortisol peaked in B (A:9.5; B:20.9; C:13.4; D:4.8 micrograms/dl), suggesting normal hypothalamic reactivity to the surgical stimulus. Finally very low GH levels were observed (A:0.04; B:0.07; C:0.06; D:0.09 ng/ml) suggesting GH deficiency, which had possibly affected the size of patient's glottis. Our data support the hypothesis that hypoglycemia in the Prader-Willi syndrome originates from inadequate lipolysis during starvation.
 ...
PMID:[General anesthesia in Prader-Willi syndrome]. 910 80

Young growing animals appear to have significantly reduced "nutritional to short periods of unstressed starvation compared with adults, with resultant growth arrest and/or atrophy of diaphragm (Dia) muscle fibers. The aim of this study was to assess in an adolescent rat model of acute nutritional deprivation (ND; 72 h) the impact of insulin-like growth factor I (IGF-I), with or without added growth hormone (GH), on the cross-sectional areas (CSA) of individual Dia muscle fibers. Five groups were studied: 1) control (Ctr); 2) ND; 3) ND given IGF-I (ND/IGF-I); 4) ND given GH (ND/GH); and 5) ND given a combination of IGF-I and GH (ND/IGF-I/GH). IGF-I was given by a subcutaneously implanted osmotic minipump (200 microg/day), whereas GH was administered twice daily by a subcutaneous injection (250 microg every 12 h). Isometric contractile and fatigue properties of the Dia were determined in vitro. Forces were normalized for muscle CSA (i.e., specific force). Dia fiber type proportions were determined histochemically, and fiber CSA was quantified by using a computer-based image-processing system. Total serum IGF-I concentrations were significantly reduced in ND and ND/GH animals, compared with Ctr, and elevated in the groups receiving IGF-I. The provision of growth factors did not alter the contractile or fatigue properties of ND animals. Dia fiber type proportions were similar among the groups. In ND animals, there was a significant reduction in the CSA of types I, IIa, IIx, and IIc Dia fibers compared with Ctr. The administration of IGF-I alone or in combination with GH to ND animals significantly diminished the reduction in Dia fiber size. GH alone had no effect on Dia fiber size in ND animals. We conclude that with acute ND the peripheral resistance to the action of GH appears to be bypassed by the administration of IGF-I alone or in combination with GH.
 ...
PMID:Effect of insulin-like growth factor I and/or growth hormone on diaphragm of malnourished adolescent rats. 910 40

It is well known that high levels of glucocorticoids cause osteoporosis and that physiologic levels of growth hormone (GH) are required for normal bone remodeling. It has been suggested that glucocorticoids regulate GH-responses via the regulation of GH-receptor expression. The aim of the present study was to investigate whether cortisol plays a role in the regulation of GH-receptor expression in cultured human osteoblasts. The effect of serum starvation and cortisol on GH-receptor expression was tested in human osteoblast (hOB)-like cells. Serum starvation for 24 h resulted in an increase in GH-receptor mRNA levels (90 +/- 1% over control culture). Cortisol increased GH-receptor mRNA levels in a dose-dependent manner with a maximal effect at 10(-6)M. The stimulating effect of cortisol on GH-receptor mRNA levels was time-dependent, reaching a peak 12 h after the addition of cortisol (126 +/- 29% over control culture) and remaining up to 12 h later. The increase in GH-receptor mRNA levels was accompanied by an increase in 125I-GH binding which reached a maximum at 24 h (196 +/- 87% over control culture). In conclusion, glucocorticoids increase GH-receptor expression in hOB-like cells. Further studies are needed to clarify whether glucocorticoid-induced regulation of the GH-receptor is important in human bone physiology.
 ...
PMID:Cortisol increases growth hormone-receptor expression in human osteoblast-like cells. 949 39

Substrate fluxes in response to growth hormone administration depend on both the calorie as well as acid-base balance. Growth hormone's acidogenic action as a consequence of promoting fatty acid utilization yields protons required for driving hepatic glutamate efflux; effective uncoupling of nitrogenous precursors from ureagenesis and recycling as glutamate bound for the periphery appears dependent upon this mechanism. Subsequent peripheral retrieval of the salvaged glutamate requires insulin-like growth factor-1 (IGF-1) activated uptake and acid-base homoeostasis. In addition to this nitrogen sparing acidogenic effect, growth hormone is also basogenic in combination with IGF-1 and acting on the kidney as a target organ. Therefore acid-base and nitrogen homoeostasis are normally attuned to one another through the co-ordinated action of growth hormone/IGF-1 on substrate fluxes. However during starvation ketoacid production as the consequence of incomplete fatty acid oxidation and ketone excretion swamps the basogenic limb and full-blown metabolic acidosis prevails; under this condition growth hormone's effectiveness in sparing nitrogen for anabolic processes is curtailed as glutamate (emanating from the liver) and glutamine (derived from muscle proteolysis) are directed to the kidneys, supporting ammoniogenesis: nitrogen balance is now sacrificed for acid-base homoeostasis. Underlying this state is an intracellular acidosis that may contribute to insulin resistance and developing hyperglycaemia in response to growth hormone. In acute injury, an additional acid load contributed from muscle proteolysis and cytokines reinforces an intracellular acidosis that further blunts growth hormone responsiveness and suppresses coupled IGF-1 production. From this perspective growth hormone's acidogenic and basogenic actions should balance for an effective anabolic response during hypermetabolic catabolic illnesses.
 ...
PMID:The role of growth hormone in substrate utilization. 958 78


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>