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)

Hepatic insulin extraction is difficult to measure in humans; as a result, the interrelationship between defective insulin secretion and insulin insensitivity in the pathogenesis of glucose intolerance in cirrhosis remains unclear. To reassess this we used recombinant human C-peptide to measure C-peptide clearance in cirrhotic patients and controls and thus derive C-peptide and insulin secretion rates after a 75-gm oral glucose load and during a 10 mmol/L hyperglycemic clamp. Cirrhotic patients were confirmed as insulin-insensitive during a euglycemic clamp (glucose requirement: 4.1 +/- 0.1 mg/kg/min vs. 8.1 +/- 0.5 mg/kg/min; p less than 0.001), which also demonstrated a low insulin metabolic clearance rate (p less than 0.001). Although intolerant after oral glucose, the cirrhotic patients had glucose requirements identical to those of controls during the hyperglycemic clamp (cirrhotic patients: 6.1 +/- 1.0 mg/kg/min; controls: 6.3 +/- 0.7 mg/kg/min), suggesting normal intravenous glucose tolerance. C-peptide MCR was identical in cirrhotic patients (2.93 +/- 0.16 ml/min/kg) and controls (2.96 +/- 0.24 ml/min/kg). Insulin secretion was higher in cirrhotic patients, both fasting (2.13 +/- 0.26 U/hr vs. 1.09 +/- 0.10 U/hr; p less than 0.001) and from min 30 to 90 of the hyperglycemic clamp (5.22 +/- 0.70 U/hr vs. 2.85 +/- 0.22 U/hr; p less than 0.001). However, with oral glucose the rise in serum C-peptide concentration was relatively delayed, and the insulin secretion index (secretion/area under 3-hr glucose curve) was not elevated. Hepatic insulin extraction was reduced both in fasting and during the hyperglycemic clamp (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relationship between insulin sensitivity, insulin secretion and glucose tolerance in cirrhosis. 206 59

The MCR of testosterone is decreased but the MCR of estradiol is unchanged in men with cirrhosis and elevated serum sex hormone-binding globulin (SHBG) concentrations. Previous studies indicated that SHBG from cirrhotic men selectively delivers estradiol, but not testosterone, to peripheral tissues of rats in vivo. These results suggest that estradiol and testosterone may bind to different SHBG isoforms in serum and that the estradiol-binding isoforms may be selectively altered in cirrhosis. This hypothesis was tested by polyacrylamide gel isoelectric focusing and fast protein liquid chromatography chromatofocusing. After Concanavalin-A affinity purification of serum glycoproteins from pregnant women, normal men, normal women, and cirrhotic men, the glycoprotein fraction was reconstituted, labeled with [3H]testosterone or [3H]estradiol, and applied to isoelectric focusing gels. Testosterone was bound selectively by the most acidic isoforms of SHBG, pI 4.5-5.4, and there was a significant anodal shift of the estradiol-binding isoforms in serum from cirrhotic men compared to that in serum from normal men. The selective binding of testosterone to the most acidic isoforms of SHBG was confirmed by fast protein liquid chromatography chromatofocusing, wherein the binding reactions were measured at neutral pH after separation of the isoforms. These biochemical studies and previous physiological experiments question the conventional view that testosterone and estradiol bind to a single competitive binding site on SHBG. Rather, testosterone is selectively bound by the most acidic SHBG isoforms. The estradiol-binding isoforms undergo a significant anodal shift in cirrhosis; this abnormality may result in the lack of decrease in estradiol MCR in cirrhosis.
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PMID:Differential binding of testosterone and estradiol to isoforms of sex hormone-binding globulin: selective alteration of estradiol binding in cirrhosis. 341 44

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

An attempt has been made to investigate drug elimination in patients with liver disease. Antipyrine was chosen as a model drug. The patients were divided into three groups depending upon clinical, biochemical, radiologic and histologic findings; (1) mild (Idiopathic portal hypertension, extrahepatic portal vein obstruction and Gilbert's syndrome); (2) moderate (Budd-Chiari syndrome and amoebic liver abscess); (3) severe (acute hepatitis, chronic active hepatitis and cirrhosis). A prolongation in antipyrine half-life (t1/2) was observed in 108 patients with liver disease (24.59 +/- 1.72 h) as compared to 12 controls (11.63 +/- 0.86 h). Similarly, metabolic clearance rate was decreased in all liver disorders. Among liver function tests, antipyrine t1/2 showed a significant correlation with serum albumin and prothrombin time index. After phenobarbitone administration, antipyrine clearance studied in 37 patients showed a significant decrease in t1/2 and an increase in MCR. Antipyrine t1/2 in 26 patients after recovery was comparable to those of controls.
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PMID:Impairment of drug elimination in patients with liver disease. 398 89

Immunological analysis of ascitic fluids from 49 patients with gastrointestinal cancer was performed and compared to those from 13 patients with hepatic cirrhosis and 3 with congestive heart failure. The analysis of ascitic fluid was performed using natural killer (NK) activity, MLR, PHA-induced lymphoproliferation (LP) and PPD-LP. Immunologic suppression by malignant ascitic fluid was more remarkably observed in PHA-LP, PPD-LP, MLR and NK assay than that by cirrhotic ascites, and it was further proved to be dose dependent. Ascitic fluids from patients with congestive heart failure showed no suppressive effects. There was no correlation between these suppressions and AFP, CEA or immunosuppressive acidic protein (IAP) levels in ascitic fluids. The first fraction of sephadex G 200 Gel filtration, which has a molecular weight of more than 200,000, showed the immunosuppressive activity. It is concluded from these results that this immunosuppressive factor does not involve AFP, CEA and IAP. Thus, it is presumed that the prognosis of the patients with gastrointestinal cancer might correlate with the immunosuppressive factor in their ascitic fluid.
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PMID:[Suppression of immunological response by ascitic fluid from gastrointestinal cancer patients]. 620 9

Simultaneous kinetic studies of 3,5-diiodothyronine (3,5-T2) and T3 were performed in 8 patients with biopsy proven cirrhosis and in 15 healthy subjects using the single injection, noncompartmental approach. The following T3 kinetic data were obtained in patients with cirrhosis and normal subjects (mean +/- SD): serum T3 (nmol/liter) 1.27 +/- 0.30 vs. 1.79 +/- 0.28 (P less than 0.001); MCR [liters X day-1 X (70 kg)-1] 22.9 +/- 5.3 vs. 26.7 +/- 4.4 (P less than 0.10); production rate [nmol X day-1 X (70 kg)-1] 29.0 +/- 9.6 vs. 47.7 +/- 9.0 (P less than 0.001). In patients with cirrhosis serum 3,5-T2 levels were reduced to 58 +/- 38% of those found in normal subjects (P less than 0.02). The MCR was unaffected, 125 +/- 85%, whereas the production rate was reduced to 57 +/- 26% (P less than 0.005). The conversion rate from T3 to 3,5-T2 was unaltered, 96 +/- 34% of that found in normals. It is concluded that reduced serum levels of 3,5-T2 in cirrhosis are due to a diminished amount of substrate, T3, and not to decreased 3'-deiodination of T3 or to an increase clearance of 3,5-T2.
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PMID:The extrathyroidal conversion of 3,5,3'-triiodothyronine to 3,5-diiodothyronine in patients with liver cirrhosis. 686 83

To evaluate the influence of changes in liver function on serum levels of melatonin, we measured serum levels and MCR of the hormone in patients with liver cirrhosis and in healthy control subjects. Daytime (0900-1100 h) serum levels of melatonin in patients with liver cirrhosis were significantly elevated compared to those in healthy subjects. Significant positive correlations of the daytime serum levels of melatonin with the serum retention rate of indocyanine green dye and serum levels of total bilirubin were noted. The clearance of melatonin from blood showed a biphasic first-order kinetic pattern. The half-life of each phase was significantly prolonged in patients with cirrhosis compared to healthy subjects. Our data indicate that the elevated daytime serum levels of melatonin in patients with liver cirrhosis are due to decreased clearance, probably related to decreased liver blood flow, lowered activity of 6 beta-hydroxylase, and competition with bilirubin in the intrahepatic transport system.
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PMID:Melatonin serum levels and metabolic clearance rate in patients with liver cirrhosis. 706 95