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

Insulin binding and insulin receptor down-regulation characteristics were evaluated, as well as cholesterol and phospholipid levels in erythrocytes from 22 patients with liver cirrhosis. These parameters were correlated with clinical characteristics and with scores related to severity of the liver injury. Nine healthy subjects were studied as a control group. It was observed that insulin binding was generally greater in patients than in controls because of an increase in surface insulin receptor numbers, rather than from a change in receptor affinities. In cirrhotic patients, the erythrocyte insulin receptors did not undergo the normal down-regulation process but, in most cases, increased in response to insulin incubation. The alterations in insulin processing characteristics were more frequent in patients with alcoholic cirrhosis and more severe liver impairment and correlated with the changes in the lipid composition of erythrocyte membranes. In particular, an increase in the cholesterol to phospholipid molar ratio and a decrease in polyunsaturated fatty acid content of phospholipids in erythrocyte membranes of cirrhotic patients was associated with impairments in insulin receptor processing. Similar changes in insulin receptor processing were observed when the molar ratio of cholesterol to phospholipid in normal erythrocytes was modified in vitro by incubation with cholesterol-rich liposomes.
 ...
PMID:Altered insulin receptor processing and membrane lipid composition in erythrocytes of cirrhotic patients. 157 65

This study investigated insulin receptor binding (number and affinity) to erythrocytes in patients with precirrhotic hemochromatosis, patients with cirrhosis, and healthy subjects. To evaluate plasma glucose and insulin levels, an oral glucose tolerance test (OGTT) was performed in all subjects. In the fasting state, all patients exhibited normal glucose levels. Precirrhotic patients showed slight impairment of glucose tolerance while cirrhotic patients were strikingly glucose intolerant. In both patient groups, fasting plasma insulin levels were increased. Following the glucose load, plasma insulin levels were significantly enhanced in precirrhotic patients at 90 and 120 min and increased at all times in cirrhotic patients. In the postabsorptive state (in the presence of hyperinsulinemia) insulin binding and the number and affinity of insulin receptors of erythrocytes were not different in precirrhotic or cirrhotic patients when compared to controls. We conclude that studies of insulin binding on erythrocytes do not contribute to the evaluation of the pathogenesis of insulin resistance in liver disease.
 ...
PMID:Insulin binding to erythrocytes in hyperinsulinemic patients with precirrhotic hemochromatosis and cirrhosis. 331 88

Coexistence of hyperinsulinemia and normal or impaired carbohydrate tolerance indicates insulin resistance which is frequently observed in patients with liver diseases such as liver cirrhosis, fatty liver, acute and chronic hepatitis and idiopathic haemochromatosis. Insulin resistance in liver diseases can be due to circulating insulin antagonists or a target tissue defect in insulin action, either due to changes in the state of the insulin receptor or due to a postreceptor defect, that means any abnormality in the insulin action sequence following the initial binding step. High insulin levels in liver diseases are caused by diminished degradation of insulin by the liver whereas hypersecretion only plays a minor role under basal conditions. High levels of glucagon, free fatty acids and growth hormone are well known in liver diseases but until now there is no evidence of the pathogenetic importance of these factors. Conflicting results on insulin binding, methodological criticism on binding data and the question whether or not diminished insulin binding on peripheral blood cells plays any physiological role make it unlikely that studies on insulin receptors of peripheral blood cells contribute to the revelation of insulin resistance in liver diseases. The clamp technique allows to quantify the sensitivity of the body to exogenous insulin. The results on liver cirrhosis in connection with studies on glucose metabolism show that under basal conditions insulin insensitivity is due to peripheral resistance (primarily muscle) according to a postreceptor defect. Finally the causes of insulin resistance in liver diseases are still not known.
 ...
PMID:[Insulin resistance in liver diseases]. 353 94

Eighteen patients with postnecrotic cirrhosis of liver, including three patients who had had a portosystemic shunt operation, and 19 normal controls were studied. The tests performed included monocyte insulin receptor assay, iv glucose tolerance test, glucagon test, and insulin tolerance test. Insulin resistance was documented by the presence of fasting hyperglycemia and glucose intolerance together with hyperinsulinemia as well as resistance to exogenous insulin. The binding of [125I]insulin to monocyte insulin receptors was significantly decreased in cirrhotic patients compared with that in controls (P less than 0.02), and this was due to a significant decrease in the high affinity association constant (P less than 0.005). There was a significant negative correlation between the fasting insulin level and maximum [125I]insulin binding in cirrhotic patients (r = -0.8; P less than 0.02). Cirrhotics that had had a shunt operation showed a higher fasting insulin level, a greater insulin resistance, and a smaller maximum [125I]insulin binding to insulin receptors than those without shunt. All of these findings suggested a down-regulatory effect of hyperinsulinemia on the monocyte insulin receptors. An impaired glycemic response to glucagon was also found in cirrhotics, the exact mechanism of which remains to be elucidated. However, as the increases in plasma cAMP after glucagon were similar in cirrhotics and controls, the fault apparently did not lie in the glucagon receptor.
 ...
PMID:Down-regulation of insulin receptors in postnecrotic cirrhosis of liver. 628 82

This report describes a 55-year-old diabetic patient with severe insulin resistance due to obesity and hepatic cirrhosis. Anti-insulin antibodies were responsible for only a minor part of the insulin resistance. Insulin resistance was mediated primarily at the target tissue level by a combination of insulin receptor deficiency and a postreceptor defect. When the patient was treated with U-500 regular pork insulin subcutaneously, her insulin requirement was only one third to one half of that during U-100 NPH or regular insulin treatment. The reasons for the greater efficacy of U-500 insulin are unknown. U-500 insulin may have a place in the optimization of therapy for patients with insulin resistance of nonimmunologic origin.
 ...
PMID:Enhanced efficacy of U-500 insulin in the treatment of insulin resistance caused by target tissue insensitivity. 636 60

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.
 ...
PMID:Insulin resistance in liver cirrhosis: decreased insulin binding to circulating monocytes. 700 94

In man, the assay of insulin receptors is performed on circulating monocytes or erythrocytes. In physiology, insulin binding decreases with age; it is lower in women during the luteal phase of the menstrual cycle or during administration of oestrogen-progestogen oral contraceptives; it exhibits diurnal variation; it increases after physical training; it depends on the diet, being inversely correlated with its carbohydrate content; finally, rapid variations in binding affinity are observed after glucose ingestion or after breakfast. In pathology, obese people are resistant to the effects of insulin and they have decreased numbers of receptors on blood cells; short-term fasting induces an increase in the binding affinity, while a long term hypocaloric diet leads to an increase in receptor numbers. Similarly non-insulin-dependent, maturity onset diabetics, even without overweight, have low numbers of binding sites, which are increased by diet or after treatment by sulfonylureas. In the syndrome of insulin resistance and acanthosis nigricans, there is a decrease in hormone binding, which is either primary (Type A) or is secondary to the effects of circulating antibodies to the insulin receptor (Type B). In acromegaly, insulinomas, liver cirrhosis and acute viral diseases the binding of insulin is decreased. On the contrary, variable results have been reported in cases of lipoatrophic diabetes, leprechaunism, uremia and glucocorticoid administration. Finally, an increase in insulin receptors has been observed in anorexia nervosa and in insulino-penic diabetes.
 ...
PMID:[The insulin receptors of the blood cells and their study in disease states in man (author's transl)]. 734 Jun 95

Liver cirrhosis is characterized by an increased incidence of glucose intolerance, diabetes and insulin resistance. We report a cirrhotic man (41 years old) who developed glucose intolerance and diabetes with insulin resistance over a period of six years. This patient suffered from severe portal hypertension with oesophageal varices and a enormously increased spleen volume. The subject underwent prophylactic endoscopic sclerotherapy of oesophageal varices. Splenectomy was performed because of severe piastrinopenia with recurrent nose bleeding. During laparotomy, multiple liver biopsies confirmed diagnosis of liver cirrhosis. Intra-operatory exploration revealed a splenic vein thrombosis. For this reason the planned spleno-renal shunting was not performed and the patient was only submitted to splenectomy. Liver function improved in the month following splenectomy and concomitant decrease of insulin resistance was observed (with a reduction in daily insulin dosage from 126 to 10 I.U.). We propose the following explanations of this event: 1) A decrease of portal and pancreatic vein pressure may have induced a proportional decrease (as already reported) of glucagon secretion. 2) The ameliorated liver function may have induced an improvement of liver glucose, insulin and glucagon metabolism. 3) A reduction of insulin circulating level (proved by a decrease of C Peptide value) may have lessened the insulin receptor down-regulation.
 ...
PMID:[Decrease of insulin resistance after splenectomy in a diabetic patient with liver cirrhosis and portal hypertension. Physiopathologic evaluation]. 784 51

We here show the application of mRNA differential display to investigate changes in gene expression in rat liver cirrhosis and address problems inherent in the technique when applied to this complex disease model. A number of differentially expressed mRNA species could be identified and two were analyzed in more detail here. One was found to derive from a new gene while the other corresponded to fetuin, a 41 kDa N-glycoprotein that specifically inhibits tyrosine kinase activity of the insulin receptor when phosphorylated. Fetuin expression was reduced by 45% in liver cirrhosis induced by bile duct ligation, but not in cirrhosis induced by carbon tetrachloride/Phenobarbital, as compared to controls. Our results raise the possibility that fetuin plays a regulatory role in the proliferation of parenchymal liver cells.
 ...
PMID:Application of mRNA differential display to liver cirrhosis: reduced fetuin expression in biliary cirrhosis in the rat. 875 72

Insulin regulates hepatocellular metabolism and growth following insulin receptor (IR) autophosphorylation and activation of the intracellular adapter protein, insulin receptor substrate 1 (IRS-1). IRS-1 activates SH2 domain proteins such as Grb2, which may be vital to hepatocyte growth. To determine if these substances are abnormally expressed under pathophysiologic conditions, IR, IRS-1, Grb2 protein, and IR mRNA were studied in normal human liver (n = 10), cirrhotic liver (n = 10), and hepatocellular carcinoma (HCC) (n = 10) that had been procured during operative procedures. IR mRNA was quantified by S1-nuclease assay using a 195-bp digoxigenin-labeled IR DNA probe and normalized to the level of expression of the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) gene. Protein concentrations were determined by immunoblot analysis following SDS-PAGE of liver homogenate samples. Labeled DNA and antibody-complexed protein were detected by chemiluminescent means and quantified by densitometric analysis (mean densitometric units +/- standard error). Similar levels of IR mRNA were observed in normal tissue, cirrhosis, and HCC. IR protein concentration was significantly greater in HCC than in normal liver (1.82 +/- 0.2 vs 1. 25 +/- 0.17; P < 0.05). IRS-1 was significantly increased in cirrhosis compared to normal liver (1.61 +/- 0.31 vs 0.86 +/- 0.21; P < 0.05). No differences were observed in Grb2 in the three tissue types. Insulin receptor overexpression, previously seen in other tumor types, may confer an insulin-mediated growth advantage in HCC if added receptors reflect functional high affinity binding sites. Although an altered mass of IRS-1 protein was not observed in HCC, an IRS-1 increase in cirrhosis may favor hepatic regeneration.
 ...
PMID:Human insulin receptor and insulin signaling proteins in hepatic disease. 1021 Jun 39


1 2 3 Next >>