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)

Receptor and post-receptor abnormalities of insulin action and their possible role in the insulin resistance of cirrhosis were examined in eight biopsy-proven cirrhotic subjects and eight age-weight matched healthy volunteers. To this end, oral glucose tolerance tests (OGTT), insulin dose response curves and insulin binding to circulating monocytes were determined for each subject. The dose-response curves for the cirrhotic subjects were significantly shifted to the right compared to the control subjects, indicating the presence of insulin insensitivity (ED50 223 +/- 30 versus 64 +/- 8 mU/l respectively; P less than 0.001). The magnitude of the right shift of the insulin-dose response curves correlated significantly (P less than 0.001) with the OGTT 2 h insulin levels (r = 0.74) and the insulin areas under the OGTT curves (r = 0.86). In contrast, insulin responsiveness was marginally elevated in the cirrhotic group (maximal glucose disposal 680 +/- 47 versus 574 +/- 21 ml/m2/min; P less than 0.05). Insulin binding to circulating monocytes was normal in the cirrhotic subjects. It is concluded that the insulin resistance of cirrhosis is due to a post-receptor defect in insulin action which reduces insulin sensitivity but not insulin responsiveness.
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PMID:Insulin resistance in cirrhosis: evidence for a post-receptor defect. 639 47

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

A systematic 20-year follow-up study of 1,221 diabetic patients was carried out in Osaka, Japan. The mean annual mortality rates were 2.55% for men and 1.64% for women. The ratios of observed to expected numbers of deaths were 1.50 for men and 1.39 for women, indicating an excess mortality for diabetic patients of both sexes, and higher mortality in men than in women. Factors that predisposed diabetic patients to premature death were early age of onset, albuminuria, diabetic retinopathy and fasting glucose level greater than 11.1 mmol/l at the initial examination. Insulin dependence was also associated with poor prognosis. Cerebro-cardiovascular and renal diseases were the major causes of death in the diabetic patients; heart disease was the cause of death in 16.9%, cerebrovascular disease in 16.4% and renal disease in 11.9%. The relatively high incidence of renal disease as cause of death in diabetic patients was striking. Malignant neoplasms of liver and of pancreas and cirrhosis were also associated with increased ratio of observed to expected number of deaths in the patients.
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PMID:A long-term follow-up study of Japanese diabetic patients: mortality and causes of death. 664 95

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

Insulin receptors and insulin stimulation of lipogenesis were studied in adipocytes from normal and cirrhotic subjects undergoing abdominal surgery. Despite the presence of hyperinsulinemia in the cirrhotic subjects, binding to receptors was not diminished compared to controls, whether expressed per cell number or cell size. Lipogenesis per cell surface area was higher basally (17.4 +/- 5.1 versus 3.8 +/- 1.6, p less than 0.05) and during maximal insulin stimulation (31.8 +/- 6.5 versus 10.4 +/0 3.9, p less than 0.01) in the cirrhotic subjects. However, cirrhotic and control adipocytes showed a similar increase above basal rates of lipogenesis with maximal insulin stimulation. The rate of lipogenesis was not correlated with fasting insulin level but was negatively correlated, basally (r = -0.61, p less than 0.05) and during maximal insulin stimulation (r = -0.52, p less than 0.05) with cell surface area. In contrast, insulin insensitivity, as quantified by ED50 for stimulation of lipogenesis, was positively correlated with fasting insulin level (r = 0.77, p less than 0.05) but was not related to cell size. It is concluded that the in vivo insulin resistance seen in cirrhosis is not due to any diminution in insulin binding or lipogenesis in adipocytes.
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PMID:Insulin action and cirrhosis: insulin binding and lipogenesis in isolated adipocytes. 675 67

1. Oral glucose-tolerance tests (100 g) were carried out in six patients with stable well-compensated cryptogenic cirrhosis and in 12 control subjects. 2. In confirmation of previous studies, patients with cirrhosis had high post-glucose serum insulin levels and were glucose intolerant (mean incremental glucose area 954 +/- 186 compared with 482 +/- 35 mmol 3 h-1 l-1 in controls; P < 0.05). 3. Forearm arteriovenous differences of glucose and forearm blood flow were measured to estimate the proportion of the glucose load metabolized in peripheral tissues. Values in cirrhotic patients and control subjects (5614 +/- 1630 compared with 5344 +/- 672 mumol of glucose min-1 l-1 of forearm in 3 h) were similar despite higher glucose levels and sustained high insulin levels in the cirrhotic patients. 4. Peak lactate concentrations after glucose were of similar magnitude in the two groups (0.66 +/- 0.12 compared with 0.62 +/- 0.75 mmol/l) but in the patients with cirrhosis the peak occurred later and was more sustained. 5. The glucose intolerance of cirrhosis is primarily due to impaired hepatic retention of the glucose load. Insulin resistance in peripheral tissues may also be important since the higher insulin concentrations found in cirrhotic patients failed to enhance peripheral glucose uptake.
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PMID:Forearm glucose uptake in cirrhosis and its relationship to glucose tolerance. 700 Apr 17

Hyperinsulinemia and insulin resistance have been reported in patients with liver cirrhosis. Since insulin receptor decrease has been demonstrated in some conditions of insulin resistance, we have studied insulin binding to circulating monocytes in eleven patients with alcoholic liver cirrhosis. Specific insulin binding at tracer concentration was lower in cirrhotics than in control subjects (p < 0.005). Insulin binding to monocytes was correlated with basal plasma insulin level in cirrhotics (r = -0.76; p < 0.01). The inhibiting effect of native insulin on 125I-insulin binding was similar in cirrhotics and controls suggesting that concentration rather than affinity of the binding sites is affected in cirrhosis of the liver. These findings suggest that decrease in insulin receptor concentration exists in liver cirrhosis, probably as a consequence of chronic hyperinsulinemia.
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PMID:Insulin resistance in liver cirrhosis: decreased insulin binding to circulating monocytes. 700 94

In order to investigate pancreatic B-cell function in hepatic cirrhosis and to elucidate the role of porto-caval shunt-circulation in the development of hyperinsulinism and hyperglucagonemia in cirrhotic patients, blood glucose, plasma insulin and glucagon, and serum C-peptide concentrations were measured during OGTT in 11 control and 16 cirrhotic subjects as well as in 7 patients with prehepatic block secondary to thrombosis of the portal vein. Insulin and glucagon levels were significantly higher in the cirrhotic than in the control group (for insulin: p less than 0.01, less than 0.001, less than 0.01 and less than 0.05 at 0, 60, 90 and 120 min, respectively; for glucagon: p less than 0.01, less than 0.01, and less than 0.05 at 0, 30 and 60 min, respectively). Serum C-peptide levels were, however, similar in the two groups with the exception of the 30-min value, which was significantly lower in the cirrhotic group (p less than 0.05). Plasma insulin and glucagon concentrations in patients with prehepatic block were similar to those of the controls but significantly lower than the values found in cirrhotic patients (for insulin: p less than 0.05 at 0, 30, 60 min, respectively). Serum C-peptide levels of these patients were not significantly different either from the control values or from those obtained in the cirrhotic group. Accordingly, pancreatic B-cell secretion is not increased in hepatic cirrhosis. Hence, the hyperinsulinism is due to decreased heptic degradation of the hormone. Decreased degradation of both insulin and glucagon should be attributed mainly to parenchymal liver damage, rather than porto-systemic shunting.
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PMID:Insulin, C-peptide and glucagon levels during OGTT in hepatic cirrhosis and in patients with prehepatic block. 704 1

1. In 37 patients with cirrhosis of the liver of different severity (11 in class A, 18 in class B, and 8 in class C, according to Child's criteria modified by Hobbs), inulin and p-aminohippurate clearances, total fractional protein excretion and the fractional clearances of alpha 1-acid glycoprotein, albumin, transferrin, alpha 2-macroglobulin and beta 2-microglobulin (in 20 patients) were determined. 2. Insulin clearance was lower than 70 ml/min in 19 patients had p-aminohippurate clearance was lower than 300 ml/min in 20 patients. Total fractional protein excretion was above normal in 19 patients; alpha 1-acid glycoprotein fractional clearance was above normal in 11, albumin fractional clearance in 10, transferrin fractional clearance in five, alpha 2-macroglobulin fractional clearance in three, and beta 2-microglobulin fractional clearance in 10. 3. The increases in protein excretion were independent of any impairment of renal tubular function. An inverse relationship between protein excretion and the clearances of inulin and p-aminohippurate was found. No difference in protein excretion was found between the three groups of patients with different degrees of liver damage. 4. The results suggest that in cirrhosis an increase in glomerular permeability is frequent, though generally slight; it is correlated with an impairment of kidney function and is independent of the severity of the liver damage.
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PMID:Proteinuria in patients with cirrhosis: relationship between renal and hepatic function. 710 34

Cirrhosis of the liver, a condition characterised by hepatocyte regeneration, is also associated with elevated insulin levels and insulin resistance. In animal models hepatic regeneration is associated with increased IGFBP-1 gene expression. Insulin is known to be an inhibitor of IGFBP-1 gene expression and circulating insulin levels in man demonstrate a negative correlation with IGFBP-1 levels. To further our understanding of the regulation of IGFBP-1 in cirrhosis we have studied steady state levels of IGFBP-1 mRNA in human liver from three groups of patients: Group 1, tissue obtained at the time of harvesting donor liver for orthotopic liver transplantation (n = 4); group 2, patients undergoing major liver resection with no histological evidence of chronic liver disease (n = 4); and group 3, patients undergoing orthotopic transplantation for chronic liver failure (n = 9). Simultaneous samples of serum were taken at the time of surgery in some patients and in these patients IGFBP-1 mRNA levels were related to circulating levels of IGFBP-1 and insulin. IGFBP-1 mRNA was detectable in all the human liver samples with the greatest levels seen from the normal livers of group 2 patients. Insulin levels were elevated in the cirrhotic group 3 patients compared to a normal range as were IGFBP-1 levels. There was no relationship between circulating levels of IGFBP-1 and IGFBP-1 gene expression. In conclusion, IGFBP-1 mRNA is present in human adult liver at the time of surgery and also in cirrhotic liver despite high levels of insulin suggesting that there are factors other than insulin regulating IGFBP-1 gene expression.
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PMID:Expression of IGFBP-1 in normal and cirrhotic human livers. 751 35


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