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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatic insulinase activity was studied in cirrhosis in an attempt to explain the hyperinsulinemia known to occur in this disease. Liver tissue was obtained during laparotomy in seven patients with cirrhosis of the liver and five patients without liver disease. Insulin degradation was significantly decreased in the cirrhotic liver at each time interval measured (p less than 0.05). Insulinase inhibitor activity was measured in the plasma of 12 patients with cirrhosis of the liver and six controls. There was no significant difference between the two groups. Decreased insulinase activity in cirrhosis may account, in part, for the hyperinsulinemia seen in this disease.
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PMID:Insulin degradation in hepatic cirrhosis. 637 64

Plasma level of immunoreactive insulin (IRI) and C-peptide (CPR), and their responses to intravenous administration of glucagon were studied in 37 patients with cirrhotic portal hypertension during hepatic vein catheterization. IRI and CPR in peripheral vein and hepatic vein were compared with development of portal vein collaterals measured by indocyanine green disappearance tests and portal venograms. In additional 2 cases, the values were compared with those of portal vein blood obtained by percutaneous transhepatic catheterization. Plasma IRI of peripheral vein in cirrhotic patients, those who had only esophageal varices but did not have remarkable amount of portal vein collateral blood flow, revealed the changes closely resembling the controls. On the contrary, peripheral vein IRI elevated significantly in cirrhotics with large shunt and the values exceeded those of hepatic vein, although responses to the glucagon test were normal. In experimental study using dogs, peripheral IRI revealed significant increase after the portocaval anastomosis diverting the portal blood containing high IRI into the inferior vena cava, and the values exceeded those of hepatic vein. It is important to know the development of portal vein collaterals as a major cause of hyperinsulinemia in liver cirrhosis.
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PMID:[Clinical and experimental studies on elevated plasma level of insulin in cirrhotic patients with portal hypertension and portosystemic collateral circulation]. 637 13

The possible contribution of hepatocellular damage and portal-systemic shunting to hyperinsulinism in cirrhosis was studied in 23 cirrhotics, 8 of whom had a surgical portacaval shunt, and 16 controls by measuring insulin and the connecting peptide (C-peptide) concentrations in simultaneous samples of peripheral arterial and hepatic venous blood. The fractional hepatic insulin extraction (0.48 +/- 0.06, mean +/- SE) was normal in cirrhosis. The hepatic insulin elimination rate was directly related to arterial insulin levels (r = 0.91, P less than 0.001) even at very high circulating levels. Extrahepatic insulin metabolism was measured across the kidney and lower limb. There were no significant differences between cirrhotics and control subjects in relation to renal (0.25 +/- 0.05 vs. 0.23 +/- 0.04) and lower limb insulin extraction (0.14 +/- 0.07 vs. 0.19 +/- 0.04). While in the control group hepatic venous insulin (0.143 +/- 0.018 pmol/ml) markedly exceeded the peripheral insulin concentration (0.083 +/- 0.009 pmol/ml, P less than 0.01), the contrary was found in cirrhotics with end-to-side portacaval shunt in whom all the pancreatic venous effluent is shunted to the systemic circulation (hepatic venous insulin, 0.130 +/- 0.028 pmol/ml; peripheral, 0.234 +/- 0.037 pmol/ml; P less than 0.01). Portal-hypertensive cirrhotics without a surgical portacaval shunt also had hepatic venous insulin levels (0.132 +/- 0.029 pmol/ml) below peripheral arterial insulin concentrations (0.205 +/- 0.041 pmol/ml, P less than 0.01). The study suggests that hyperinsulinism in cirrhosis is not the result of an intrinsic defect of hepatic insulin metabolism but of the spontaneous shunting of portal blood to the systemic circulation.
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PMID:Role of spontaneous portal-systemic shunting in hyperinsulinism of cirrhosis. 638 74

To study beta-cells response during liver cirrhosis, OGTT (0.75 g/kg b.w.) was performed in 7 cirrhotic patients (histologically diagnosed). An impaired glucose tolerance was observed in all the subjects: basal plasma glucose was 0.74 g/l +/- 0.05 (M +/- SEM); at 90 min was 1.50 g/l +/- 0.10, and at 180 min was 1.10 g/l +/- 0.17. Plasma insulin peak was delayed at 90 min (78.2 microU/ml +/- 27.7); two patients showed basal hyperinsulinemia. C peptide concentration reached the peak at 120 min (3.6 ng/ml +/- 0.5), in agreement with Gragnoli and coll. Plasma insulin concentration did not correlate with hepatic laboratory findings. All the patients had severe liver disease, including esophageal varices; in 4 patients ascites was observed. The results show that impaired glucose tolerance in patients with liver cirrhosis is not directly related to the degree of the disease and confirm the decreased insulin catabolism and peripheric resistance.
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PMID:[Beta-cell activity during the oral glucose tolerance test in subjects with hepatic cirrhosis]. 638 29

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

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

To elucidate the relative contribution of parenchymal liver damage and spontaneous portal-systemic shunting to the reduction of peripheral insulin degradation rate and the decrease in plasma concentrations of three branched chain amino acids (valine, leucine, and isoleucine), plasma insulin, C-peptide, and amino acid concentrations were measured during oral glucose tolerance tests in 17 patients with liver cirrhosis, 10 with idiopathic portal hypertension, 5 hospitalized controls, and normal subjects. None of the patients had evidence of hepatic encephalopathy. Patients with idiopathic portal hypertension had histologically minimum hepatic fibrosis in spite of the existence of extensive exophageal varices. The molar ratio between plasma concentrations of C-peptide and insulin was significantly decreased in patients with cirrhosis, but not in those with idiopathic portal hypertension. In both patients with cirrhosis and idiopathic portal hypertension, the three branched chain amino acid levels were significantly decreased and the molar ratio between the concentrations of the three branched chain amino acids and two aromatic amino acids (tyrosine and phenylalanine) were markedly reduced. These results suggest that spontaneous portal-systemic shunting does not primarily contribute to the reduced degradation of insulin, but has a close relationship with the decrease in branched chain amino acid levels and in the molar ratio of plasma amino acids. In addition, the present data indicate that decreased branched chain amino acid levels in patients with cirrhosis is not merely ascribed to hyperinsulinemia and that the decrease in the molar ratio of plasma amino acids is not specific to the presence of hepatic encephalopathy.
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PMID:Effect of spontaneous portal-systemic shunting on plasma insulin and amino acid concentrations. 698 17

A patient with biopsy-proved biliary cirrhosis and previous gastrojejunostomy and portacaval anastomosis experienced episodes of severe hypoglycemia. She was found to have hyperinsulinemia and hyperglucagonemia. An oral glucose tolerance test showed postgastrectomy hypoglycemia. Results of the intravenous tolbutamide test were diagnostic for insulinoma, but results of the intravenous glucagon test and prolonged fast (96 hours) were not. Failure, on two occasions, to suppress C-peptide normally during insulin-induced hypoglycemia led to a diagnosis of pancreatogenous hyperinsulinemia. The pancreas showed a 10-fold increase in islet volume, with intensely positive staining with anti-insulin and anti-glucagon antiserums in addition to anti-somatostatin and anti-pancreatic polypeptide antiserums. Incidental findings at pancreatic exploration were a mesothelioma, which did not stain with anti-insulin antiserum, and, at autopsy one year later, a hepatoma.
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PMID:Diagnosis of pancreatic islet hyperplasia causing hypoglycemia in a patient with portacaval anastomosis. 699 72

We studied the relationship between the pancreatic glucoregulatory hormones, insulin and glucagon, and glucose intolerance through the response to food and intravenous glucose in 11 patients with verified hepatic cirrhosis. Blood samples were obtained from the portal vein and the superior vena cava. The results of the systemic vein hormone determinations were compared to results obtained from peripheral vein determination in 10 age-, sex- and weight-matched controls admitted to hospital for minor surgery and to results from ambulant, normal subjects. In the cirrhotics collateral shunting was elevated by transhepatic portography. The cirrhotics and the matched controls had similar glucagon levels and responses, but showed hyperresponsiveness to a meal compared to ambulant normal subjects. Compared to the matched controls the cirrhotics showed glucose tolerance and hyperinsulinism, but compared to normal subjects the hospitalized controls were also glucose intolerant and demonstrated hyperinsulinism. In the cirrhotics, the portal vein/vena cava ratio for insulin was negatively correlated to the degree of collateral shunting. No relationship was found between the degree of portosystemic shunting and fasting concentrations of glucagon and insulin, and the insulin response to glucose. The glucagon response to the meal, was correlated to severity of cirrhosis. The rate constant for glucose disappearance (K-value) was not related to the insulin response, to severity of disease or to degree of shunting. It was, however, correlated to the suppressibility of glucagon secretion as measured in the portal vein. Our results indicate that the glucoregulatory disturbances in compensated cirrhosis are partly caused by non-specific factors which are independent of cirrhosis; the portal-vein hormone responses, however, support the contention that glucagon secretion influences glucose tolerance in cirrhotics.
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PMID:Pancreatic glucoregulatory hormones in cirrhosis of the liver: portal vein concentrations during intravenous glucose tolerance test and in response to a meal. 699 1


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