Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of the present investigation was to determine whether endogenously produced interleukin (IL)-1 mediates the changes in insulin-like growth factor (IGF) I and IGF binding proteins (IGFBP) induced by chronic abdominal sepsis in rats and to correlate the changes in the IGF system with the alternations in protein synthesis. A constant infusion of IL-1 receptor antagonist (IL-1ra) was begun after the induction of sepsis and was continued for 5 days. Sepsis decreased IGF-I levels in the blood, liver, and gastrocnemius muscle, increased the content in the kidney, and did not alter IGF-I levels in heart, jejunum, and spleen. IL-1ra attenuated the sepsis-induced decrease in plasma IGF-I and completely prevented the changes in IGF-I observed in liver, kidney, and the gastrocnemius. IGFBP-1 was increased in the blood, liver, and muscle of septic rats. IL-1ra prevented this increase in IGFBP-1 in blood and liver but not in muscle. The rate of in vivo protein synthesis was decreased in the gastrocnemius and kidney and unaltered in the heart, liver, jejunum, and spleen. A strong linear correlation existed between levels of IGF-I and the rate of protein synthesis determined simultaneously in the gastrocnemius. These results provide evidence for the role of IL-1 as an endogenous mediator of the sepsis-induced changes in IGF-I and IGFBP-1 and suggest that the accompanying changes in muscle protein synthesis are partially mediated via changes in IGF-I.
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PMID:IL-1 receptor antagonist attenuates sepsis-induced alterations in the IGF system and protein synthesis. 863 89

The purpose of the present study was to determine whether insulin-like growth factor (IGF)-I would increase whole body and muscle glucose uptake in septic rats that are known to be insulin resistant. Animals were infused with either saline, low-dose IGF-I, high-dose IGF-I, or a maximally stimulating dose of insulin for 2 h, and the glucose metabolic response was assessed using a euglycemic clamp in combination with [3-3H]glucose. Under basal conditions, sepsis increased the rates of whole body glucose uptake, glycolysis, and hepatic glucose production. Under euglycemic hyperinsulinemic conditions, septic rats demonstrated a marked insulin resistance as evidenced by the impaired rate of insulin-stimulated glucose uptake and muscle glycogen synthesis. In contrast, the infusion of either dose of IGF-I increased total glucose uptake, glycolysis, and glycogen synthesis in both control and septic rats to the same extent. Furthermore, there was no difference in the IGF-I stimulation of glucose uptake (as determined by [14C]-2-deoxyglucose) in the gastrocnemius, soleus, and heart between control and septic rats. These results indicate that the glucose metabolic response to IGF-I is intact in insulin-resistant septic rats.
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PMID:IGF-I stimulates muscle glucose uptake during sepsis. 882 Oct 99

Malnutrition is a critical predictor of mortality and morbidity in children with biliary atresia who undergo orthotopic liver transplantation. Growth hormone (GH) enhances nitrogen retention in patients with chronic obstructive lung disease, sepsis, and in fasted adult volunteers. The goal of this study was to assess the acute response to recombinant human GH (rhGH) treatment in children with biliary atresia to determine whether GH therapy was likely to improve pretransplant nutritional status. Five children, aged 10-32 months, with biliary atresia and persistent cholestasis despite surgical attempts to reestablish bile flow, were studied. All five children had portal hypertension, conjugated hyperbilirubinemia, and decreased serum albumin concentrations. Length, weight, and growth velocity were decreased in all five children. Despite adequate energy and protein intake, fat stores were depleted in all five subjects, and somatic protein stores were diminished in all except one child. Baseline serum concentrations of insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) were low (8.4 +/- 2 ng/ml and 0.2 +/- 0.1 mg/l respectively). In the four children who completed the study, serum IGF-I and IGFBP-3 levels did not change after treatment with rhGH (0.1 mg/kg/day) for 4 days. Our findings indicate that children with biliary atresia awaiting liver transplantation are insensitive to GH and that treatment with GH is unlikely to promote anabolism. A rationale exists for examining the effect of treatment with IGF-I, which mediates the anabolic effects of GH.
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PMID:Growth hormone insensitivity in children with biliary atresia. 885 79

The metabolic response to trauma and sepsis involves an increased loss of body proteins. Specific sites of changes of protein and amino acid metabolism have been identified. In skeletal muscle, the rate of proteolysis is accelerated greatly. The rate of protein synthesis also may be increased but not enough to match the increase in degradation. Intramuscular glutamine concentration is decreased because of increased efflux and possibly decreased de novo synthesis. In the liver, the rate of synthesis of selected proteins (i.e., albumin, transferrin, prealbumin, retinol-binding protein, and fibronectin) is decreased, whereas acute phase protein synthesis is accelerated. Tissues characterized by rapidly replicating cells, such as enterocytes, immune cells, granulation tissue, and keratinocytes, exhibit early alterations in the case of decreased protein synthesis capacity. In these tissues, glutamine use is accelerated. Increased stress hormone (cortisol and glucagon) and cytokine secretion, as well as intracellular glutamine depletion, are potential mediators of altered protein metabolism in trauma and sepsis. However, the relative importance of these factors has not been clarified. Therapy of acute protein catabolism may include the use of biosynthetic human growth hormone, possibly in combination with insulin-like growth factor-1, and the administration of metabolites at pharmacologic doses. We recently studied the effects of carnitine and alanyl-glutamine administration in severely traumatized patients. We found that both carnitine and the glutamine dipeptide restrained whole-body nitrogen loss without affecting selected indices of protein metabolism in the skeletal muscle.
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PMID:Metabolic response to injury and sepsis: changes in protein metabolism. 929 Jan 10

We report on a patient with Nevo syndrome manifesting intrauterine and postpartum overgrowth, accelerated osseous maturation, dolichocephaly, highly arched palate, large, low-set ears, cryptorchidism, delayed neuropsychological development, hypotonia, adema, contractures of the hands and feet, a single a transverse palmar crease, and tapering digits. After meningococcal sepsis at age 6 months, he remained decerebrate. Thereafter, overgrowth and especially weight gain were extremely accelerated until his death at age 18 months, at which time his height was 103 cm and his weight was 23 kg. In addition to low plasma concentrations of growth hormone and insulin-like growth factor, severe insulin resistance was observed. It is presumed that a selective defect in insulin-stimulated glucose uptake, with preservation of anabolic effect, was one of the causes of his "overgrowth without growth hormone," at least in the last 12 months of life after severe brain damage.
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PMID:Nevo syndrome. 950 68

Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) may be beneficial against the protein catabolism seen in injury and septicemia. Further understanding of their effects on carbohydrate metabolism is needed. In a septic porcine model receiving total parenteral nutrition, pretreatment with GH or IGF-1 (or no treatment in controls) was followed by an infusion of live Escherichia coli bacteria. Endogenous glucose production, carbohydrate oxidation, glucose and lactate fluxes over the liver, gastrointestinal organs, kidney, and hindleg were determined. Endogenous glucose production increased during septicemia in the GH group. The metabolic acidosis induced by septicemia was augmented by GH, but attenuated by IGF-1. The alanine and lactate levels were significantly higher in the GH- than in the IGF-1 treated animals during septicemia. IGF-1 pretreatment appeared to induce favorable effects while GH pretreatment might produce unfavorable effects on carbohydrate metabolism in septic piglets.
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PMID:Treatment with growth hormone and insulin-like growth factor-1 in septicemia: effects on carbohydrate metabolism. 956 41

Inflammatory cytokines may mediate the host response to infection via central nervous system, endocrine, and/or paracrine/autocrine signaling mechanisms. Previous studies have shown that intravenous administration of interleukin (IL)-1 beta alters the concentration of the anabolic hormone insulin-like growth factor (IGF)-I in plasma and various tissues. The purpose of the present study was to determine 1) whether the intracerebroventricular injection of IL-1 beta can influence peripheral IGF-I levels in control animals and 2) whether the central administration of a IL-1 receptor antagonist (IL-1ra) can prevent the changes in peripheral IGF-I induced by endotoxin [lipopolysaccharide (LPS)] or sepsis produced by cecal ligation and puncture. In the first experiment, injection of IL-1 beta (100 ng/rat) decreased IGF-I levels in plasma, liver, and gastrocnemius muscle 28-36% by 1.5 h in conscious fasted rats. IGF-I levels remained reduced at 3 h, but returned to baseline by 6 h. IGF-I content was not altered in soleus, kidney, spleen, intestine, or whole brain after IL-1 beta. In the second series of experiments, LPS injected intravenously decreased IGF-I levels in plasma, liver, and gastrocnemius at 1.5 h, and levels were even further reduced at 3 and 6 h in these tissues (59, 57, and 48%, respectively). Moreover, the IGF-I content was also decreased in soleus (30-35%) and increased in kidney (2- to 3-fold) after LPS. In the third experiment, changes in IGF-I levels in plasma and tissues, similar to those seen in LPS-treated rats, were detected 24 h after induction of peritonitis. Intracerebroventricular infusion of IL-1ra did not alter any of the changes in IGF-I produced by either LPS or sepsis, although it did attenuate the concomitant changes in growth hormone levels. These data suggest that, although central IL-1 beta is capable of modulating peripheral IGF-I levels, central administration of IL-1ra was unable to modulate the changes in peripheral IGF-I in blood and tissues produced by either endotoxemia or peritonitis.
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PMID:Role of central IL-1 in regulating peripheral IGF-I during endotoxemia and sepsis. 957 56

The hypercatabolic response to trauma, extensive surgery and sepsis is characterized by an increased metabolic rate, severe muscle wasting and a negative nitrogen balance. This process of 'autocannibalism' may be in part a consequence of a disordered growth hormone (GH)/insulin-like growth factor (IGF) axis. In this chapter the normal physiology of the GH/IGF axis is first briefly reviewed. This is followed by a discussion of the changes that accompany fasting and catabolic illness, the effects of IGF-1 administration in health and disease and a comparison of the effects of IGF-1, GH and insulin on catabolism. Although initial investigations of IGF-1 administration in animals and human volunteers have often been encouraging, studies in catabolic patients have so far proved disappointing. Combined treatment with GH, IGF-1 (and insulin) or with IGF-1 and its major binding protein, may prove more effective, especially when used in conjunction with nutritional supplements such as glutamine.
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PMID:The role of IGFs in catabolism. 958 77

Sepsis induces a state of growth hormone (GH) resistance associated with a decrease of circulating insulin-like growth factor (IGF) I, a GH-dependent anabolic hormone mainly produced by the liver. To address the mechanisms that might trigger GH insensitivity in sepsis, we investigated the regulation of liver GH receptor (GHR) and its gene expression by endotoxin. Endotoxin injection in rats decreased serum IGF-I and liver GH-binding sites after 10 h. In contrast to liver GHR, circulating GH-binding protein (GHBP) levels were not significantly reduced after endotoxin injection. The parallel decrease in IGF-I and GHR and in their corresponding liver mRNAs suggests that decreased serum IGF-I and liver GHR were likely to result from decreased liver synthesis. Although GH administration in control animals significantly enhanced serum IGF-I, it did fail to prevent the decline in serum IGF-I and liver GH-binding sites in endotoxemic rats. In this study, we showed that endotoxin injection induces a state of GH insensitivity associated with decreased liver GHR. This decline in GHR, which cannot be prevented by exogenous GH, might contribute to the GH insensitivity observed in sepsis.
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PMID:GH insensitivity induced by endotoxin injection is associated with decreased liver GH receptors. 1007 25

Acquired growth hormone resistance (AGHR) may be defined as the combination of a raised serum growth hormone (GH) concentration, low serum insulin-like growth factor-1 (IGF-1) concentration and a reduced anabolic response to exogenous GH. A wide range of conditions exhibit the syndrome to a variable degree, including sepsis, trauma, burns, AIDS, cancer, and renal or liver failure. The primary defect seems to be a reduction in IGF-1 concentration which then leads to increased GH concentration by a loss of negative feedback. It is not clear whether IGF-1 concentration falls because of decreased production or increased clearance from the circulation, or both. Treatment to reverse the biochemical defect by restoring IGF-1 levels, either by the administration of GH or IGF-1, has resulted in improvements in a wide range of metabolic parameters and, more recently, to definite clinical benefit in well-defined groups, such as patients with AIDS. These results cannot be extrapolated to other groups with AGHR as a recent unpublished report suggested increased mortality in critically ill patients treated with GH. Research needs to focus on the molecular basis of AGHR if we are to develop therapies for catabolism.
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PMID:Acquired growth hormone resistance in adults. 1008 99


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