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)

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.
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PMID:Insulin binding to erythrocytes in hyperinsulinemic patients with precirrhotic hemochromatosis and cirrhosis. 331 88

Hyperinsulinemia in human cirrhosis is generally considered an expression of reduced hepatic insulin degradation. To determine whether hyperinsulinemia may also depend on an altered feedback inhibition of insulin secretion, we performed euglycemic hyperinsulinemic clamp studies, infusing 40, 372, or 1280 mU/m2 X min biosynthetic human insulin in 30 compensated cirrhotic patients with portal hypertension and impaired glucose tolerance and 25 normal subjects, matched for age, sex, and weight. Mean fasting plasma insulin was significantly higher in cirrhotic patients [26.1 +/- 2.3 vs. 12.4 +/- 0.6 (+/- SE) microU/ml; P less than 0.001], while fasting plasma glucose levels were similar in the 2 groups. The mean plasma C-peptide level was significantly higher in cirrhotic patients, both basally (2.7 +/- 0.1 vs. 1.7 +/- 0.1 ng/ml; P less than 0.001) and during the clamp studies. Suppression of C-peptide at 120 min of the clamp was significantly less in cirrhotic patients (37 +/- 7% vs. 79 +/- 4%, 52 +/- 9% vs. approximately 100%, and 54 +/- 4% vs. approximately 100% during the 40, 372, and 1280 mU/m2 X min insulin infusions, respectively). The fasting C-peptide to insulin molar ratio was significantly lower in cirrhotic patients (5.4 +/- 0.3 vs. 6.4 +/- 0.3; P less than 0.005). The MCR of insulin at the three steady states was not significantly different between the 2 groups, whereas the basal systemic delivery rate of insulin was significantly higher in cirrhotic patients (14.7 +/- 1.7 vs. 6.5 +/- 0.4 mU/m2 X min; P less than 0.001). These results suggest that reduced feedback inhibition of insulin secretion may contribute to the hyperinsulinemia associated with cirrhosis.
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PMID:Feedback inhibition of insulin secretion is altered in cirrhosis. 352 9

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.
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PMID:[Insulin resistance in liver diseases]. 353 94

In the past 10 years we have examined 20 children with inflammatory liver disease associated with high serum titers of anti-liver-kidney microsome antibody (anti-LKM). The first hepatic symptoms were progressive fatigue and jaundice, the fortuitous finding of hepatomegaly or splenomegaly with raised transaminase activity, or an acute hepatitis-like illness. At the time of diagnosis, hepatomegaly was present in 18 children, splenomegaly in 16, jaundice in nine, and ascites in two. Serum alanine transferase activities were elevated in all but two, who had already received steroids. Serum total gammaglobulin values were greater than 2.0 gm/dl in 16 children, prothrombin activity less than or equal to 60% in six, and serum titer of anti-LKM between 1:100 and 1:100,000. All children but one had cirrhosis, and histologic signs of aggressivity were present in 14. In 11 children one or more extrahepatic diseases were present, including type 1 diabetes, vitiligo, glomerulonephritis, autoimmune hemolytic anemia, hypoglycemia with hyperinsulinism, autoimmune thyroiditis, chronic mucocutaneous candidiasis with hypoparathyroidism, and multiple cutaneous and visceral telangiectasias. Treatment with prednisone and azathioprine improved the liver condition in 16 of the 18 patients given treatment. In eight of them discontinuation of treatment resulted in rapid relapse; 14 are still receiving treatment and have stable hepatic function with follow-up from 8 months to 6 1/2 years. Only two are free of treatment. Four children died, two in spite of immunosuppressive therapy, one during a relapse, and one of extrahepatic disease. These results indicate that this autoimmune inflammatory liver disease may have onset early in life, with several clinical patterns; is frequently associated with certain types of extrahepatic manifestations of autoimmune origin; and is a potentially fatal disease for which immunosuppressive treatment must be started early.
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PMID:Liver disease associated with anti-liver-kidney microsome antibody in children. 395 Aug 19

One hundred consecutive patients with nonautoimmune chronic active hepatitis (51% HBsAg-positive), 50 patients with cirrhosis (38% HBsAg-positive), 25 patients with chronic persistent hepatitis, and 118 patients with hepatoma who were seen at this hospital were reviewed to determine the prevalence and characteristics of glucose intolerance and diabetes in these conditions. Diabetes (fasting serum glucose greater than 7.8 mmol/L, 140 mg/dl on two separate occasions) was present in 8% of patients with chronic persistent hepatitis and mild chronic active hepatitis, 44% of patients with severe chronic active hepatitis, 40% of patients with cirrhosis, and 15% of patients with hepatoma, compared with 7% of all other patients aged 35 yr or over, undergoing liver biopsy. Compared with this high prevalence of diabetes in liver disease, only 3% of diabetic patients referred to the hospital diabetic clinic had chronic hepatitis or cirrhosis. Glucose tolerance was similar in chronic active hepatitis and cirrhosis and was characterized initially by basal hyperinsulinemia, normal basal glucose levels but elevated serum glucose following glucose loading, and evidence of insulin resistance. We suggest that the high prevalence of diabetes in chronic active hepatitis and cirrhosis in Saudi Arabia is due to the insulin resistance of chronic liver disease acting over many years in a population with a high genetic predisposition to diabetes.
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PMID:Diabetes mellitus in chronic active hepatitis and cirrhosis. 608 43

By immunofluorescence and double labelled anti sera L and M pyruvate kinase, there is a double localization of isozymes. It is detected in basal state, in vitro, in isolated hepatocyte, in vivo in experimental or genetic (Zucker rat) hyperinsulinemia or in regenerating liver following partial hepatectomy. It is found in hepatology, in regenerative nodule of cirrhosis and in cancerous cells of liver. This double presence of L and MPK tallies with a specific double hormonodependence: induction of MPK by insulin, and inhibition of LPK by glucagon.
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PMID:[L and M isoenzymes of hepatic pyruvate kinase and their hormone dependence]. 622 Jul 89

In order to investigate disturbances in glycoregulation and plasma amino acids and their possible relationship in alcoholic liver diseases, plasma concentrations of insulin, C-peptide, glucagon and branched-chain (valine, leucine, isoleucine) as well as aromatic (phenylalanine, tyrosine) amino acids were measured during an arginine test (i.v infusion of arginine chloride 0.5 g/kg over 30 min) in 21 alcoholic patients: 11 with cirrhosis (group C) and 10 with steatosis (group S). Insulin responses to arginine was reduced in both groups, whereas glucagon response was increased in group C and reduced in group S. Plasma concentrations of branched-chain amino acids were reduced in both groups, irrespective of the degree of hyperinsulinism. Plasma concentrations of aromatic amino acids were increased only in cirrhotic patients; the increase was independent of the degree of hyperglucagonism and of the plasma insulin/glucagon molar ratio. These results suggest that disturbances of glycoregulation in plasma amino acids imbalance do not play a major role in alcoholic cirrhosis and steatosis.
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PMID:[Disturbances in glycoregulation and plasma amino acids in alcoholic hepatopathies. Study using the arginine test]. 623 16

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.
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PMID:Down-regulation of insulin receptors in postnecrotic cirrhosis of liver. 628 82

Patients with hepatic cirrhosis often have demonstrable glucose intolerance. We studied 21 patients with cirrhosis of the liver. Oral glucose tolerance tests (OGTT), intravenous arginine stimulation tests (IVAST), and intravenous insulin tolerance tests (IVITT) were performed, and timed blood samples were obtained for the assay of glucose immunoreactive insulin (IRI), C-peptide (C-P), and immunoreactive glucagon (IRG). The 125I-insulin binding to circulating monocytes was studied in some of the patients. All results were compared to those of similar studies performed on healthy controls. During OGTT significant glucose intolerance was demonstrable in the patients with cirrhosis (2 hr plasma glucose 198.8 +/- 14.3 mg/dl in cirrhosis and 116.4 +/- 4.2 in controls; p less than 0.001). Two-hour plasma IRI, C-P, and IRG were significantly higher in the cirrhotic patients than in controls (p less than 0.001; less than 0.001; less than 0.025). In response to IVAST, the patients with cirrhosis showed a greater first-phase insulin secretion and controls had a slightly better second-phase insulin release. Plasma IRG rose from a basal value of 446 pg/ml to 1100 in the patients with cirrhosis and from 171 pg/ml to 494 in controls. After intravenous insulin administration, there was only a 40% decline in plasma glucose concentration from basal values in the patients with cirrhosis whereas the controls showed a 60% decline, demonstrating that the patients with cirrhosis had significant insulin resistance. Moreover, the half-life of insulin was prolonged in the patients with cirrhosis (t 1/2 = 15.5 min in cirrhosis and 10.3 in controls; p less than 0.001); and the ratio of C-P to insulin during OGTT was also reduced, indicating that the patients with cirrhosis have reduced hepatic clearance of insulin. The specific binding of 125I-insulin to circulating monocytes was 2.7% in cirrhosis, 2% in obese controls, and 4% in lean controls. There was a significant negative correlation between the fasting plasma insulin values and the specific binding of insulin. In conclusion, patients with hepatic cirrhosis have significant glucose intolerance characterized by hyperinsulinemia, hyperglucagonemia, insulin resistance, and down-regulation of insulin receptors. Although hyperinsulinemia is probably caused by reduced hepatic clearance of insulin, hyperglucagonemia is primarily due to increased pancreatic secretion.
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PMID:Studies of glucose intolerance in cirrhosis of the liver. 635 38

Plasma glucagon, insulin and glucose concentrations, and liver function tests were determined after an overnight fast in 24 normal subjects and 50 male cirrhotic patients. In cirrhotic patients with normal liver profiles, plasma glucagon remained within normal limits, irrespective of the presence of portasystemic anastomoses either pathological or surgical. Hyperglucagonemia was documented in presence of advanced liver dysfunction alone. Significant correlations were established between plasma glucagon and several liver function tests, i.e., serum bilirubin, albumin/globulin ratio, and prothrombin time. Moreover, hyperglucagonemia normalized on recovery from clinical manifestations and improvement in liver profile. Plasma insulin was raised primarily in the presence of a significant portasystemic shunting and maximum levels were observed in patients manifesting advanced liver dysfunction as well. However, no correlation was evident between plasma insulin and any of the liver function tests. Fasting plasma glucose was not altered in cirrhotic patients. Therefore, it is concluded that in hepatic cirrhosis, glucagon secretion by pancreatic alpha-cell may be dependent on the severity of the hepatocellular damage whereas portasystemic shunting may be responsible for hyperinsulinemia which may be further exaggerated in presence of advanced liver dysfunction.
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PMID:Hyperglucagonemia in hepatic cirrhosis: its relation to hepatocellular dysfunction and normalization on recovery. 636 96


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