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)

In the present investigation, insulin sensitivity and fasting levels of insulin, C-peptide, glucagon, growth hormone and free fatty acids were estimated and correlated in a population of individuals suffering from liver cirrhosis or chronic hepatitis. Insulin sensitivity, assessed by glucose disappearance rate after intravenous bolus injection of insulin, was reduced but not significantly different from controls in subjects with chronic persistent hepatitis, while it was significantly reduced in individuals suffering from chronic active hepatitis or liver cirrhosis. Insulin, glucagon, growth hormone, and free fatty acid fasting levels were higher than in healthy subjects in individuals with liver cirrhosis or chronic active hepatitis but not in subjects with chronic persistent hepatitis. C-peptide concentrations did not differ from controls in subjects with liver disease. Significant negative correlations occurred between coefficients of insulin sensitivity and fasting concentrations of insulin, glucagon, growth hormone and free fatty acids, but not with fasting levels of C-peptide. Positive relationships were present between fasting levels of free fatty acids and both glucagon and growth hormone concentrations. These results show that, unlike subjects with liver cirrhosis and chronic active hepatitis, individuals suffering from chronic persistent hepatitis do not differ from healthy subjects in insulin sensitivity and fasting levels of insulin, glucagon, growth hormone, and free fatty acids. Moreover, they suggest that both hyperinsulinemia and high concentrations of counterregulatory substances might play a role in the pathogenesis of insulin resistance in subjects suffering from chronic liver disease.
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PMID:Possible roles of insulin, glucagon, growth hormone and free fatty acids in the pathogenesis of insulin resistance of subjects with chronic liver diseases. 639 73

Circulating hormone and metabolite profiles have been studied in ten patients with alcoholic cirrhosis, five patients with alcoholic hepatitis and/or fatty liver, and nine normal controls over a 12-h period of meals and activity. Blood glucose was elevated throughout the day in both cirrhotic and non-cirrhotic alcoholics (mean 12-h glucose; controls 5.38 +/- 0.16 (SEM) mmol/l; cirrhotics 6.98 +/- 0.30 mmol/l, P less than 0.001; non-cirrhotics 7.18 +/- 0.26 mmol/l, P less than 0.001). Non-cirrhotic alcoholics had an exaggerated insulin response to meals, whereas cirrhotic patients had hyperinsulinaemia throughout the day (mean 12-h insulin; controls 16.3 +/- 2.3 mU/l; cirrhotics 35.8 +/- 6.6 mU/l, P less than 0.02). Growth hormone levels were elevated only in patients with cirrhosis (mean 12-h growth hormone, 7.06 +/- 1.35 v. 0.85 +/- 0.17 micrograms/l, P less than 0.001). Serum cortisol was persistently elevated in cirrhotics but only in the evening in non-cirrhotic alcoholics. Lactate and pyruvate responses to meals were exaggerated in non-cirrhotic patients whereas in cirrhotics, levels were persistently raised. Blood glycerol was elevated in all alcoholic patients whereas ketone body levels were normal. Hypertriglyceridaemia was observed only in non-cirrhotic patients. No relationship between the endocrine and metabolic state was observed in either cirrhotic or non-cirrhotic patients.
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PMID:Hormone and metabolite profiles in alcoholic liver disease. 641 54

To explore the influence of extrahepatic factors in the pathogenesis of insulin resistance in hepatic cirrhosis, we studied 125I-insulin binding to erythrocytes and monocytes of 14 clinically stable cirrhotic individuals and compared the results with a normal control group. All patients had fasting normoglycemia at the time of the study but abnormal glucose tolerance was detected in 7 of 9 cirrhotic patients after an oral glucose load. Seven patients (group N) had normal fasting serum insulin levels, and 7 patients (group H) manifested fasting hyperinsulinemia. However, all patients had elevated insulin levels after oral glucose. Insulin binding to erythrocytes was significantly decreased in both cirrhotic subgroups; monocyte studies in 5 hyperinsulinemic patients revealed a similar decrease in binding. Scatchard analysis in monocytes suggests that this decreased binding is secondary to a decrease in the receptor number per cell. No correlation between insulin binding and fasting plasma insulin, glucagon, or growth hormone levels was seen. Sera from 4 patients were examined for the presence of a non-specific inhibitor of insulin binding, but no evidence for such a factor was found. We conclude that the decrease in insulin binding is mediated in the monocyte by a reduction of receptor concentration; in the erythrocyte the mechanism for decreased binding could not be clearly delineated. The insulin resistance seen in cirrhosis may result in part from decreased binding of insulin to target tissues; an additional postreceptor defect cannot be excluded in hyperinsulinemic individuals.
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PMID:Insulin resistance and insulin receptors in hepatic cirrhosis. 675 26

Chronic liver disease is associated with raised basal and TRH-stimulated PRL and GH levels. In a recent study we found the kidney to be the main site of prolactin elimination in patients with liver disease. In order to determine whether this is specific for PRL or a more general mechanism for polypeptide removal, we studied the elimination of GH, which resembles PRL in molecular weight and primary amino acid sequence, in 5 patients with portal hypertension and hepatic cirrhosis and 5 patients with noncirrhotic portal hypertension. Plasma GH levels were measured before and after TRH in peripheral, hepatic and renal vein samples, taken during diagnostic hepatic vein catheterization. An excessive paradoxical increase of GH after THR stimulation was found in 4 out of 5 cirrhotic patients but in none of the noncirrhotic individuals (p less than 0.025). After TRH the mean hepatic venous levels were significantly lower than the peripheral venous levels in 4 out of 5 noncirrhotic patients but in only 1 of the 5 cirrhotic patients (p less than 0.05). The mean renal vein GH levels were significantly lower than the peripheral levels in 3 out of 5 noncirrhotic patients and in none of the cirrhotic patients. In 2 patients in whom renal and hepatic plasma flow was measured, renal extraction of GH was found to be 0 to 6.4 micrograms, while liver extraction amounted to 22.1 and 34.7 micrograms of GH during the same 60-min period. Despite the similarity in molecular weight and primary amino acid sequence between PRL and GH, GH appears to be mainly taken up by the liver while PRL is mainly eliminated by the kidney in this group of patients with portal hypertension. This suggests that the renal elimination of prolactin is not solely dependent on glomerular filtration. The selective hepatic removal of growth hormone is probably related to a specific action of growth hormone on liver metabolism.
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PMID:Peripheral elimination of growth hormone in chronic liver disease. 680 53

The growth hormone (GH) response to apomorphine HCl (Apo) (0.75 mg sc), a dopamine (DA) receptor agonist, was assessed in healthy chronic alcoholics without cirrhosis (N = 20) and in patients with alcoholic cirrhosis both with (N = 5) and without (N = 14) hepatic encephalopathy (HE). A significant number of cirrhotic patients with (P less than 0.004) and without (P less than 0.002) HE had an impaired GH response (peak increment less than 5 ng/ml) compared with non-cirrhotic individuals. An impaired GH response was independent of the presence of HE. The magnitude of the GH response was unrelated to plasma oestrone, oestradiol, or progesterone concentrations but was significantly correlated with plasma testosterone levels (P less than 0.01). None of the patients with an abnormally low testosterone concentration showed a normal GH response. None of the subjects with HE showed an arousal response to Apo. These results suggest that DA receptor sensitivity is decreased in liver cirrhosis and that this decrease is related to inadequate circulating levels of testosterone. The occurrence of HE is independent of impaired DA function. The present study only evaluates DA function in the hypothalamic-pituitary axis and therefore may not reflect changes in other regions of brain.
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PMID:Hypothalamic-pituitary dopaminergic function in hepatic failure in man. 706 15

In 64 patients suffering from chronic inflammatory liver disease (alcoholic hepatitis, chronic active hepatitis, chronic persistent hepatitis) significantly increased values of blood glucose and insulin, free fatty acids and C-peptide were observed during a 100 g oral glucose load. Fasting values of blood glucose, free fatty acids and C-peptide were also increased, while serum growth hormone remained unchanged. In patients with chronic active hepatitis the C-peptide/insulin-ratio, a measure for hepatic insulin degradation, was significantly lowered after glucose uptake. During oral load there were no discernible differences between the different types of chronic inflammatory liver disease concerning blood glucose, serum insulin and free fatty acids. In normal weight and in overweight patients suffering from liver disease blood glucose and serum insulin values were increased to the same extent. As it is known from the liver cirrhosis chronic inflammatory liver disease lead to an insulin resistance, to which elevated free fatty acid levels contribute. Increased body weight has no influence on the insulin resistance observed in chronic liver inflammation. From the changes of the C-peptide and the C-peptide/insulin-ratio it can be deduced, that the hyperinsulinism in patients with chronic inflammatory liver disease is due to both insulin hypersecretion and diminished hepatic insulin degradation.
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PMID:[Hyperinsulinaemia and impaired glucose tolerance in chronic inflammatory liver disease (author's disease)]. 722 67

Plasma glucagon and growth hormone concentrations were measured fasting and after oral glucose in 19 patients with portal vein block with extensive portal-systemic shunting but minimal liver cell damage, 11 cirrhotic patients and 12 matched control subjects. Portal vein block patients and controls had similar fasting glucose and glucagon levels (glucose 3.8 +/- 0.1 mmol/l VS control 3.4 +/- 0.1 mmol/l (mean +/- SEM); glucagon 57.5 +/- 9.1 pg/ml VS control 51.3 +/- 7.8 pg/ml). Cirrhotic patients were hyperglycaemic (cirrhosis 4.3 +/- 0.2 mmol/l VS control 3.4 +/- 0.1 mmol/l, p < 0.01) with significantly elevated glucagon levels (167.3 +/- 61.1 pg/ml VS control 51.3 +/- 7.8 pg/ml, p < 0.05), which suppressed towards control values after oral glucose. There was no correlation between fasting plasma glucagon levels and the degree of portal-systemic shunting in cirrhotic patients. There was a strong correlation between fasting plasma glucagon concentrations and aspartate transaminase levels (r = 0.68; p < 0.01) in cirrhotic and portal vein block patients. Significant elevations of growth hormone were seen only in cirrhotic patients. It is concluded that hyperglucagonaemia is a feature of hepatocellular damage rather than portal-systemic shunting but the relationship between elevated glucagon and growth hormone concentrations and carbohydrate intolerance in cirrhosis remains unclear.
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PMID:Hyperglucagonaemia in cirrhosis. Relationship to hepatocellular damage. 741 64

Two growth hormone-binding proteins (GHBPs), one with high and the other with low affinity, have recently been described in the blood of humans and several other species. The high-affinity GHBP represents a circulating fragment of the GH receptor, encompassing its extracellular domain. The molecular nature of the low-affinity GHBP is not known in detail. GHBPs form complexes with circulating GH, prolong its biological half-life, restrict its distribution in the body, and modulate the binding of GH to receptors in tissues. Their net effect in vivo is to enhance GH action. The level of high-affinity GHBP in plasma probably reflects receptor concentrations in tissues. The level/activity of GHBP is linked to GH action, and several congenital or acquired conditions with altered GHBP levels are characterized by parallel changes in GH action (Laron-type dwarfism, pygmy dwarfism, malnutrition, obesity, insulin-dependent diabetes mellitus, liver cirrhosis, renal insufficiency). The GHBP/receptor level is nutritionally regulated, with levels low in undernutrition and high in overnutrition. Regulation of lean body mass anabolism/catabolism at the level of the GHBP/receptor provides a rational explanation for the derangements in the GH axis and their biological consequences (retarded or accelerated somatic growth) observed in nutrition disorders.
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PMID:Growth hormone-binding proteins in plasma. 750 16

The liver is the major source of circulating insulinlike growth factor-I (IGF-I) and has been suggested as a major source of at least two of the major binding proteins that modify its bioavailability. We aimed to assess the direct effects of liver dysfunction on serum levels of IGF-1 and its major binding proteins by measuring fasting levels of growth hormone, IGF-1, IGFBP-1, IGFBP-3, insulin, C peptide, and glucose in 35 patients with cirrhosis and during an oral glucose tolerance test in 16 of those patients. Serum levels of growth hormone (GH) were high in the patients: median, 12.0 mU/L (range, 1 to 87) compared with normals, 0.95 mU/L (0.1 to 20) (P < .0005) and serum IGF-1 levels were low: 81 ng/mL (38 to 153) versus 193 ng/mL (151 to 235) (P < .0001). Serum IGFBP-3 levels were low in the patients: 1.59 mg/L (0.46 to 4.43) compared with normals, 5.41 (4.34 to 6.11) (P < .0001), and there was a significant negative correlation between IGFBP-3 levels and Childs Pugh score (r = .63 P < .0001). Fasting IGFBP-1 levels were significantly higher in the patients 31 ng/mL (11 to 92) than normals, 14 (7 to 20) (P < .0001). There was no correlation between fasting insulin and IGFBP-1 levels despite high fasting insulin levels. A decrease in IGFBP-1 levels was seen during the glucose tolerance test (GTT) in all patients. In conclusion, there are significant changes in the levels of two of the major IGF-1 binding proteins that may further limit the bioavailability of already low circulating IGF-1 levels. Substrate availability appears to be a stronger influence on fasting IGFBP-1 levels than does insulin, and the close correlation of IGFBP-3 with liver function indicates a dominant regulatory role of the hepatocyte.
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PMID:Growth hormone, insulinlike growth factor-1, and insulinlike growth factor binding proteins 1 and 3 in chronic liver disease. 753 22

As growth hormone possesses anabolic properties that are active on protein metabolism, and thus of potential benefit to patients with chronic liver disease, we determined the metabolic effects of recombinant human growth hormone on insulin-like growth factor-I (IGF-I) its specific binding proteins, and liver function. Twenty consecutive patients with cirrhosis were randomized to recombinant human growth hormone (Norditropin, 4 I.U. twice daily) subcutaneously for 6 weeks (n = 10) or conventional medical treatment (n = 10). The serum concentrations of insulin-like growth factor-I in the recombinant human growth hormone group increased after 3 (p < 0.01) and 6 weeks (p < 0.02), whereas no significant changes were observed in the control group. The change in insulin-like growth factor-I during the treatment period was expressed as area under the curve (AUC). The AUCIGF-I was significantly larger in the recombinant human growth hormone group (median AUCIGF-I: 12.1, range: 0.0-54.7 weeks.nmol/l) than in the control group (median AUCIGF-I: 0.2, range: -10.6-9.9 weeks.nmol/l) (p < 0.007). Insulin-like growth factor binding protein-3 concentrations increased in the recombinant human growth hormone treated patients as well as in controls, whereas no change in insulin-like growth factor binding protein-1 concentrations was found. No significant changes were seen in the area under the curve for biochemical liver function tests. We conclude that administration of recombinant human growth hormone induces an increase in very low levels of insulin-like growth factor-I, even in patients with cirrhosis with advanced disease, but the clinical benefits remain to be demonstrated.
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PMID:Short-term effect of recombinant human growth hormone in patients with alcoholic cirrhosis. 753 20


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