Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cirrhosis is characterized by paradoxical growth hormone secretion in response to glucose and insulin infusion. To ascertain whether this abnormality contributes to insulin resistance, euglycemic hyperinsulinemic glucose clamps were performed on six patients with cirrhosis and six normal control subjects. Each patient with cirrhosis underwent two clamps in random order, a clamp with somatostatin (250 micrograms/hr) together with insulin and glucagon replacement, and a control clamp without somatostatin. The normal subjects underwent the control clamp only. During the control clamp, growth hormone levels were considerably higher in the patients with cirrhosis (6.1 +/- 0.4 vs. 0.5 +/- 0.4 mU/L, p < 0.02), and glucose uptake was considerably lower (3.29 +/- 0.56 vs. 9.52 +/- 1.14 mg/kg/min, p < 0.001). Indirect calorimetry indicated that the defect was accounted for by lower nonoxidative glucose disposal (1.23 +/- 0.45 vs. 6.00 +/- 0.73, p < 0.001). Peripheral glucose uptake, exemplified by forearm glucose uptake (0.27 +/- 0.04 vs. 1.22 +/- 0.42 mg/100 ml/min, p < 0.02), and calculated insulin sensitivity (24 +/- 8 vs. 114 +/- 20 microliters/kg/min per mU/L) were particularly diminished. In the patients with cirrhosis somatostatin suppressed growth hormone levels (6.1 +/- 1.2 to 1.2 +/- 0.4 mU/L, p < 0.05). However, no significant changes occurred in whole-body glucose uptake (3.29 +/- 0.56 vs 3.01 +/- 0.54 mg/kg/min), forearm glucose uptake (0.27 +/- 0.04 vs 0.30 +/- 0.01 mg/100 ml/min) or insulin sensitivity (24 +/- 8 vs, 35 +/- 10 microliters/kg/min/mU/L, p = 0.42).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Growth hormone, insulin-like growth factor-1 and insulin resistance in cirrhosis. 790 78

High serum concentrations of growth hormone (GH) were found in five patients with chronic liver diseases, including auto-immune chronic active hepatitis (two cases), Budd-Chiari syndrome, primary biliary cirrhosis and hepatitis B virus associated cirrhosis. Mean levels of GH were 27.8 units (normal up to 5). In three patients elevated prolactin levels were also found (mean 37.3 units for two females, normal up to 20), and 36 units in one male (normal up to 9). No other endocrine disorders were found. Although the association of raised GH levels in patients with alcoholic cirrhosis is well known, its occurrence in patients with non-alcoholic chronic liver disease is not fully established. We describe the effect of the disease course, and steroid treatment on GH levels in one patient with auto-immune chronic active hepatitis, and propose possible mechanisms for this elevation.
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PMID:Elevated growth hormone levels in patients with non-alcoholic chronic liver disease. 821 92

Basal serum growth hormone (GH) levels are elevated and insulin-like growth factor 1 (IGF-1) concentrations in serum are suppressed in patients with chronic liver disease. The aim of this study was to measure the urinary GH (U-GH) excretion and IGF-1 concentrations in patients with cirrhosis and to correlate these both to clinical and biochemical characteristics and survival rate. Urinary GH excretion, IGF-1, and other biochemical parameters were measured in 36 patients with alcoholic cirrhosis, while in the control group of 34 healthy individuals only U-GH excretion was measured. U-GH excretion was significantly higher in patients than in the healthy controls (p < 0.00001), and increased with deteriorating liver function assessed by modified Child-Turcotte score (p < 0.01). The highest U-GH excretions were found in patients with hepatic encephalopathy (p < 0.003). IGF-1 levels were reduced in cirrhosis and correlated with liver function (p < 0.001). Serum IGF-1 concentrations below 3.1 nmol/l were associated with a poor prognosis (p < 0.004). The elevated U-GH in patients with alcoholic cirrhosis may reflect high serum levels of GH due to increased pituitary secretion or decreased hepatic degradation of GH. In addition, the IGF-1 levels reflect the degree of hepatic insufficiency and, thus, seem to provide new prognostic information.
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PMID:Urinary growth hormone (U-GH) excretion and serum insulin-like growth factor 1 (IGF-1) in patients with alcoholic cirrhosis. 831 59

Nocturnal glucose administration might prevent gluconeogenesis and concomitant protein loss due to hepatic glycogen depletion. In this study the effects of nocturnal oral glucose supplements on nitrogen metabolism were investigated in 8 cirrhotic patients and in 8 healthy controls. During the night, either polymeric glucose was given or water as placebo. In the patients with cirrhosis on placebo, nitrogen balance was not different from controls: -63 +/- 8 vs. -55 +/- 4 mg N/kg b.wt./9 h (mean +/- SEM). Cirrhotic patients had increased nocturnal protein turnover rates (measured with 15N-glycine) and increased early morning levels of free fatty acids (FFA), lactate, insulin, glucagon and growth hormone. After glucose, nitrogen balance improved by 36% in the cirrhotic group, with a decrease in protein turnover rates and a decrease in plasma levels of beta-hydroxybutyrate, urea and glucagon. In the controls, glucose had no effects on nitrogen balance, on protein turnover or on the hormone levels, except for reduced FFA and ketone body levels. These data show that nocturnal calorie supplements improve nitrogen balance during the night in cirrhotic patients but not in healthy controls. Long interprandial intervals should be avoided in cirrhotic patients.
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PMID:Nocturnal oral glucose supplementation. The effects on protein metabolism in cirrhotic patients and in healthy controls. 831 66

This article analyzes 57 reports published in the years 1983 through 1964 that addressed the issue of the renal hemodynamic response to an oral protein load. Seventy-three groups are reported in those studies: 52 were healthy subjects (n = 627) and 21 had renal disease (n = 256); 47 were studied using inulin (n = 407 healthy people and 112 renal patients); 26 groups were studied using creatinine (n = 220 healthy people and 144 renal patients). Patients with liver cirrhosis were also analyzed. There was great heterogeneity in methodology used, emphasizing the need for standardization. The role of plasma amino acids, glucagon, insulin, growth hormone, PGE2, 6-ketoPGA1 alpha, brain-gut peptides, ANP, AVP, dopamine, and kinins in promoting the renal hemodynamic response to an oral protein load is discussed.
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PMID:Renal response to an acute oral protein load in healthy humans and in patients with renal disease or liver cirrhosis. 852 46

The aim of this study was to investigate the regulation of various proteins of the GHIGF axis during progression of liver failure and to search for potential prognostic markers of functional hepatic reserve. Serum levels of growth hormone (GH) and high affinity growth hormone binding protein (GHBP), insulin-like growth factor I (IGF-I) and IGF binding proteins (IGFBP) -1, -2 and -3 were determined in patients with liver cirrhosis. A continuous decline in the concentrations of IGF-I, IGFBP-3 and serum GH-binding activity (GHBP) was observed during progression of cirrhosis and the data correlated significantly with choline esterase, total serum protein and the Child score. In addition, GHBP showed a significant correlation with the enzymatic activity of glutamate dehydrogenase or transaminases and seems so to be influenced by the degree of liver cell damage. In contrast, IGFBP-1 and IGFBP-2 levels were significantly elevated in preterminal disease suggesting an upregulatory mechanism is still effective in this situation. Only when liver function had markedly deteriorated, the serum levels of these two parameters decreased again, possibly due to an impaired synthesis. The excellent correlation between the serum levels of IGF-I (r = -0.64, p < 0.001) or IGFBP-3 (r = -0.67, p < 0.001) and the Child score index suggests that they reflect the hepatic functions just as conventional indicators. For an appropriate interpretation of the liver function the measurement of the growth related peptides can be a valuable tool to estimate pathological alteration in the functional hepatic reserve or in the glucose homeostasis.
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PMID:Regulation of growth hormone (GH), insulin-like growth factor (IGF)I, IGF binding proteins -1, -2, -3 and GH binding protein during progression of liver cirrhosis. 853 56

Secretion of growth hormone (GH) is excessive in acromegaly, but also in a number of other pathological states such as anorexia nervosa, insulin-dependent diabetes mellitus (IDDM), liver cirrhosis, depression, renal failure and GH-insensitivity syndrome. Abnormalities in the neuroendocrine control of GH secretion and/or a state of insensitivity to GH contribute to hypersecretion of GH in these states, with the possible exception of acromegaly, which appears to be a primary pituitary disease. GH hypersecretion may also occur in neonates or adolescents with tall stature, thus reflecting particular physiological or paraphysiological conditions. In the cohort of brain neurotransmitters, catecholamines and acetylcholine reportedly play a major role in the control of neurosecretory GH-releasing hormone (GHRH) and somatostatin (SS)-producing neurons, and hence GH secretion. Activation of alpha 2-adrenoceptors or of muscarinic cholinergic receptors in the hypothalamus stimulates GH release, probably through stimulation of GHRH and inhibition of SS release, respectively. Activation of dopamine receptors likewise stimulates GH release, while activation of beta-receptors inhibits GH release through stimulation of hypothalamic SS function. This review discusses the involvement of brain catecholamines and acetylcholine in GH hypersecretory states, including anorexia nervosa, acromegaly, IDDM, liver cirrhosis, depression, renal failure and GH insensitivity syndrome, with a view to providing a fuller understanding of their pathophysiology and, whenever possible, diagnostic and therapeutic implications.
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PMID:Involvement of brain catecholamines and acetylcholine in growth hormone hypersecretory states. Pathophysiological, diagnostic and therapeutic implications. 858 28

Decreased serum insulin-like growth factor (IGF-I) levels have been shown in malnutrition and liver diseases. To analyse which of them is the main cause of GH-IGF-I axis alterations, serum levels of growth hormone (GH), growth-hormone releasing factor (GHRH), IGF-I and its binding protein IGFBP-3 were measured in 85 hospitalized alcoholics (51 without cirrhosis, 15 with compensated cirrhosis and 19 with cirrhosis with ascites) and in 25 healthy controls. Liver function tests and objective nutritional assessment were also performed. Serum IGF-I and IGFBP-3 levels were lower in alcoholics, particularly in those with liver cirrhosis. Serum GH was raised in cirrhotics with ascites but GHRH levels were not significantly altered. Although these patients were frequently malnourished there was no relationship between data derived from GH-IGF-I axis and nutritional parameters. However, there was a significant positive correlation between serum GH concentrations and impaired liver function and a significant negative correlation between serum IGF-I and IGFBP-3 and impaired liver function. This suggests that, in this population, serum IGF-I and IGFBP-3 levels reflect liver dysfunction rather than malnutrition.
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PMID:Effects of alcohol and liver cirrhosis on the GH-IGF-I axis. 867 9

Hyperinsulinemic euglycemic clamps were performed on six patients with compensated alcoholic cirrhosis and on six normal comparison subjects. As in previous studies, glucose uptake in the cirrhotic patients was only 21% of the comparison value. The cirrhotic patients had high growth hormone (GH) and low insulin-like growth factor-I (IGF-I) levels, with low insulin-like growth factor-binding protein (IGFBP)-3 levels, but surprisingly high IGFBP-I levels (26.8 +/- 8.4 microgH vs. 3.2 +/- 0.2 microm/L, P < .001). The log IGFBP-1 level was inversely correlated with the log insulin sensitivity (r = -.95). The clamps were repeated with a somatostatin infusion to suppress GH secretion. IGFBP-1 increased in both groups, especially in the cirrhotic subjects. Insulin sensitivity increased in the normal subjects but was unchanged in the cirrhotic patients. Following GH treatment (0.13 U/kg/d for 5 days), the clamps were repeated. GH, IGF-1, and IGFBP-3 levels were now similar in the two groups; IGFBP-1 levels decreased in the cirrhotic patients but remained fivefold higher than the comparison value (10.6 +/- 3.7 vs. 2.1 +/- 0.4, P < .05). Glucose uptake in the cirrhotic patients remained only 29% of the comparison value, but the change in their insulin sensitivity was inversely correlated with the change in their IGFB-1 levels (r = -.84). These results suggests an important role for IGFBP-1 in modulating insulin sensitivity in cirrhosis.
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PMID:High insulin-like growth factor binding protein 1 levels in cirrhosis: link with insulin resistance. 870 51

Patients with cirrhosis of the liver require an increased amount of protein to achieve N balance. However, the utilization of protein with increased protein intake, i.e. the slope from regression analysis of N balance v. intake, is highly efficient (Nielsen et al. 1995). In the present study, protein requirement and protein utilization were investigated further by measuring protein synthesis and degradation. In two separate studies, five or six patients with cirrhosis of the liver were refed on a balanced diet for an average of 2 or 4 weeks. Protein and energy intakes were doubled in both studies. Initial and final whole-body protein metabolism was measured in the fed state by primed continuous [15N]glycine infusion. Refeeding caused a statistically significant increase of about 30% in protein synthesis in both studies while protein degradation was only slightly affected. The increase in protein synthesis was associated with significant increases in plasma concentrations of total amino acids (25%), leucine (58%), isoleucine (82%), valine (72%), proline (48%) and triiodothyronine (27%) while insulin, growth hormone, insulin-like growth factor (IGF)-I and IGF-binding protein-3 were not changed significantly. The results indicate that the efficient protein utilization is due to increased protein synthesis, rather than decreased protein degradation, and suggest that increases in plasma amino acids may be responsible for the increased protein synthesis. A comparison of the patients who had a normal protein requirement with the patients who had an increased protein requirement suggests that the increased protein requirement is due to a primary increase in protein degradation. It is speculated that this is due to low levels of IGF-I secondary to impaired liver function, since initial plasma concentration of IGF-I was about 25% of control values and remained low during refeeding.
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PMID:Effect of long-term refeeding on protein metabolism in patients with cirrhosis of the liver. 913 67


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