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)

Hypergastrinemia and hyperglucagonemia follow portacaval shunt (PCS) or cirrhosis in man and experimental animals. The cause is unknown although portal diversion and hepatic dysfunction are suggested. In these studies transhepatic techniques were used to define the hepatic handling of basal and arginine-stimulated gastrin and glucagon levels in sham-operated and portacaval-shunted pigs and in a group of pair-fed sham-operated pigs. After PCS, basal gastrin levels were lower than those in sham-operated animals but were also lower in the pair-fed group, suggesting that the change resulted from partial starvation. Arginine-stimulation caused a rise in hepatic venous levels in PCS and in pair-fed pigs and in portal venous levels in sham-operated pigs. These data also suggested a response to diminished intake in PCS pigs. There was an immediate transitory rise in portal immunoreactive glucagon (Unger 30K) after PCS and a subsequent rise from the 4th postoperative day in all circulations. Arginine stimulation caused in sham-operated and PCS pigs a biphasic rise in the portal circulation and a later rise in the arterial circulation in PCS pigs. These data suggest that the effect of PCS upon gastrin levels is associated with the impaired appetite while the effect upon glucagon is the result of diversion past the liver.
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PMID:Transhepatic hormone levels in the portacaval shunted pig--the effects of arginine upon gastrin and glucagon release. 29 Feb 69

Carnitine is synthesized from lysine and methionine. In the rat, inadequate intake of either of these essential amino acids causes carnitine depletion. Inasmuch as protein deficiency is common in the hospital population, we have investigated the possible occurrence of nosocomial carnitine deficiency. Fasting serum carnitine concentration was measured in 16 normal and 247 patients in 16 disease groups. Normal range of carnitine was 55-103 muM. Only the cirrhotic group showed significant (P < 0.05) hypocarnitinemia. 14 of 36 hospitalized cirrhotics had subnormal values for serum carnitine. The creatinine/height index, midarm muscle circumference, and triceps skin-fold thickness indicated protein-calorie starvation in the 14 hypocarnitinemic liver patients. In six of the hypocarnitinemic cirrhotics (average serum level 50% of normal), spontaneous dietary intakes of carnitine, lysine, and methionine were measured and found to be only 5-15% as great as in six normocarnitinemic, healthy controls. When these six cirrhotic and six normal subjects were given the same lysine-rich, methionine-rich, and carnitine-free nutritional intake, the normals maintained normal serum carnitine levels and excreted 100 mumol/day, whereas the cirrhotics' serum level fell to 25% of normal, and urinary excretion declined to 15 mumol/day. Seven hypocarnitinemic cirrhotics died. Postmortem concentrations of carnitine in liver, muscle, heart, kidney, and brain averaged only one-fourth to one-third those in corresponding tissues of eight normally nourished nonhepatic patients who died after an acute illness of a 1-3-day duration. THESE DATA SHOW THAT CARNITINE DEPLETION IS COMMON IN PATIENTS HOSPITALIZED FOR ADVANCED CIRRHOSIS, AND THAT IT RESULTS FROM THREE FACTORS: substandard intake of dietary carnitine; substandard intake of lysine and methionine, the precursors for endogenous carnitine synthesis; and loss of capacity to synthesize carnitine from lysine and methionine.
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PMID:Deficiency of carnitine in cachectic cirrhotic patients. 89 75

Energy metabolism is abnormal in patients and experimental animals with liver cirrhosis. To help better understand the abnormalities, fuel homeostasis and carnitine metabolism were studied in fed and 24-hr-starved rats with secondary biliary cirrhosis induced by bile duct ligation for 4 wk. Plasma ketone body concentrations were decreased by 67% in starved, bile duct-ligated rats compared with control rats. In contrast, plasma nonesterified fatty acid concentrations were not different between bile duct-ligated and control rats in the fed or the fasted state. Plasma triglyceride concentrations showed the expected decrease with starvation in control rats, but were increased with starvation in bile duct-ligated rats. Urinary excretion of dicarboxylic acids was increased in both fed and fasted bile duct ligated-rats compared with the respective control groups. Compared with control rats, hepatic total carnitine content (per gram of liver) was increased by 24% in fed and by 36% in fasted, bile duct-ligated rats. Fed, bile duct-ligated rats had an increased short-chain acylcarnitine-to-carnitine ratio in liver, plasma and urine compared with control rats. Analysis of the hepatic coenzyme A pool showed decreased coenzyme A content in fed and fasted bile duct-ligated rats compared with control rats. Hepatic long-chain acylcarnitine and long-chain acyl-coenzyme A content increased with starvation both in control and bile duct-ligated rats. The rise in plasma nonesterified fatty acid concentration and hepatic long-chain acylcarnitine and long-chain acylcoenzyme A contents with starvation in bile duct-ligated rats are consistent with unaltered hepatic availability of fatty acids.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fuel homeostasis and carnitine metabolism in rats with secondary biliary cirrhosis. 193 97

Glucose homeostasis and fatty acid metabolism are abnormal in patients with cirrhosis. To assess the metabolic response to starvation in an animal model of cirrhosis, glycogen and fuel metabolism were characterized in rats with CCl4-induced cirrhosis studied 2 wk after 10 weekly doses of CCl4. Plasma concentrations of glucose and beta-hydroxybutyrate were not different between fed CCl4-treated and control rats, but plasma nonesterified fatty acid concentrations were higher in cirrhotic animals (0.25 +/- 0.01 vs. 0.39 +/- 0.04 mmol/L; p less than 0.05). After 12 hr of starvation, the plasma nonesterified fatty acid concentration had reached 0.58 +/- 0.04 mmol/L in CCl4-treated rats, compared with 0.38 +/- 0.04 mmol/L in control rats (p less than 0.05). The redistribution of the hepatic carnitine pool toward acylcarnitines, which is characteristic of starvation, was complete after fasting for 12 hr in the CCl4-treated rats, compared with the 24 hr required in control rats. In fed cirrhotic rats, liver glycogen content per gram liver was decreased by 64% compared with control rats (30.0 +/- 5.1 vs. 10.8 +/- 1.1 mg/gm liver wet wt; p less than 0.05). After 12-hr fasting, hepatic glycogen content had fallen to 14.3 +/- 3.9 and 4.8 +/- 0.4 mg/gm liver wet wt (p less than 0.05) in control and cirrhotic animals, respectively. To further characterize the status of glycogen metabolism in cirrhotic livers, activities of glycogen synthase and glycogen phosphorylase were determined. Hepatic active and total glycogen phosphorylase activities normalized to hepatocellular content were unaffected by CCl4 treatment, whereas total glycogen synthase activity was increased by 45%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Decreased hepatic glycogen content and accelerated response to starvation in rats with carbon tetrachloride-induced cirrhosis. 195 69

To evaluate the metabolic consequences of short-term (i.e., less than 24 hours) starvation, glucose and fat metabolism were studied in eight healthy subjects and in eight patients with stable cirrhosis after 16-hour and again after 22-hour starvation by 3-[3H]glucose and [14C]palmitate turnover and by indirect calorimetry. Although patients and controls showed significant increases in free fatty acid concentration (respectively, 48% +/- 12% and 53% +/- 17%) and turnover (55% +/- 14% and 71% +/- 21%) during short-term starvation, the values after 16- and after 22-hour starvation were higher in cirrhosis. Fat oxidation was enhanced in the patients, but did not increase during fasting in contrast to controls (increase 19% +/- 17%, P less than 0.05). Net glucose oxidation was decreased in postabsorptive cirrhotics (P less than 0.05). Although postabsorptive glucose turnover was not different from controls, starvation induced a greater decrease in glucose turnover in the patients (25% +/- 3% vs. 10% +/- 3%, P less than 0.05). This was not reflected in plasma glucose concentrations. In conclusion, the effects of starvation on glucose and fat metabolism are enhanced in cirrhosis; fasting hypoglycemia is prevented by decreased use of glucose. It remains to be established whether these changes are merely explained by defective liver function, per se.
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PMID:Glucose and fat metabolism during short-term starvation in cirrhosis. 199 94

Energy expenditure and substrate oxidation rate for fat, glucose and protein were evaluated by indirect calorimetry in 20 normal individuals, 35 patients with acute hepatitis and 22 patients with biopsy-proven alcoholic cirrhosis in the postabsorptive state. Measurements were done in the resting state after an overnight fast (10 to 12 hr). Oxygen consumption (ml/min/1.73 m2) in normal subjects, in patients with acute hepatitis and in patients with cirrhosis was 206.5 +/- 4.0 (mean +/- S.E.M.), 216.4 +/- 4.7 and 228.8 +/- 7.1 (p less than 0.05 vs. controls), respectively. When related to body surface area (kcal/min/1.73 m2), resting energy expenditure did not differ between normal subjects (0.98 +/- 0.02), patients with acute hepatitis (1.03 +/- 0.02) and cirrhotic patients (1.06 +/- 0.03). However, when related to 24-hr urinary creatinine excretion as an estimate of lean body mass, energy expenditure was increased in cirrhosis (p less than 0.0001). In cirrhosis an inverse association between the severity of liver disease according to Pugh and oxygen consumption and resting energy expenditure was found. In cirrhotic patients the percentages of total calories derived from fat (86% +/- 5%), carbohydrate (2% +/- 4%) and protein (12% +/- 1%) were different from those of normal controls who metabolized 45% +/- 4%, 38% +/- 4%, 17% +/- 1%, respectively. In acute hepatitis no alterations in metabolism could be found apart from a decreased protein oxidation rate. In conclusion no appreciable changes in energy metabolism exist in acute hepatitis. The pattern of fuel use in cirrhosis resembles that in starvation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Energy metabolism in patients with acute and chronic liver disease. 210 37

To investigate insulin action in muscle and adipose tissue in hepatic cirrhosis, a recently described animal model was used. Dimethylnitrosamine administration induced histologically proven cirrhosis. Contrary to expectation, muscle strips from cirrhotic rats displayed increased insulin sensitivity both with respect to glycogen synthesis (ED50 0.11 +/- 0.01 vs 0.23 +/- 0.04 nmol/l; p less than 0.03) and glucose oxidation (ED50 0.36 +/- 0.07 vs 0.97 +/- 12 nmol/l; p less than 0.02). As the cirrhotic rats had failed to gain weight normally, it is postulated that a state of relative starvation accounted for the enhanced insulin sensitivity. These data demonstrate that the severe insulin resistance characteristically associated with cirrhosis is reversible. Control of nutritional state in future studies upon DMNA induced cirrhosis should permit detailed examination of the cellular mechanisms controlling insulin sensitivity in hepatic cirrhosis.
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PMID:Insulin sensitivity in experimental cirrhosis. 267 70

About 90 per cent of morbidly obese patients show histological abnormalities of the liver. One third of patients have fatty change involving more than 50 per cent of hepatocytes. Fatty liver disease can be divided into four histological groups: Fatty liver, fatty hepatitis, fatty liver with portal fibrosis, and cirrhosis. Most patients show only fatty change. Alcohol, drugs, diabetes, poor nutrition, and weight-reducing surgery contribute to progressive liver damage, but morbid obesity alone may lead to severe disease showing all the features of alcoholic hepatitis and may end in cirrhosis and liver failure. The accumulation of fat alone is unlikely to be the stimulus to inflammation and fibrosis. Only one fifth of patients have complaints that arise from the liver. The development of severe fatty liver disease may also be asymptomatic and rarely shows the florid picture associated with alcoholic hepatitis. There is poor correlation of liver function test results with morphology in obesity. ALT levels exceeding twice the normal limit have some predictive value for histological grades of severity, but they are present in few patients. Pericentral and pericellular fibrosis in prebypass liver biopsies may be an important prognostic lesion for the development of fatty hepatitis and cirrhosis. In contrast with the frequent progression to massive fatty change, inflammation and fibrosis after bypass surgery, weight loss by low-calorie dieting, or starvation is accompanied by improvement in fatty change and return of liver function tests to normal.
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PMID:Fatty liver disease in morbid obesity. 331 4

The development of siderosis of liver and spleen was investigated in rats subjected alternately to periods of starvation and periods of feeding of diets rich in iron (0.71% or 1.23% Fe) or of control diets, during periods ranging up to 245 days. With 0.71% iron in the diet, cyclic starvation-feeding markedly enhanced the accumulation of iron in rat livers by comparison to feeding ad libitum even though rats fed ad libitum ingested far greater total amounts of iron than cyclically fed rats. With 1.23% iron in the diet, the concentration of iron in livers reached more or less the same plateau in cyclically starved-fed rats and in rats fed ad libitum (betwen 4 and 5 mg Fe/g wet weight); but the mean rate of accumulation of iron in the livers of cyclically starved and fed rats was more than twice that in rats fed ad libitum, whereas mean ingestion of iron per feeding day was only 16% higher in the former group. Surgical removal of the spleen enhanced the accumulation of iron in the liver in cyclically starved-fed rats and in rats fed ad libitum. Histologically, siderosis of the liver was moderate in rats fed the diet with 0.71% iron but was severe in rats fed the diet with 1.23% iron and most severe in those without spleens. Stainable iron was deposited in hepatocytes and in Kupffer cells. None of the rats developed cirrhosis of the liver. The data suggest that in rats a barrier to the absorption of iron from the gut, or to its later utilization, is surmounted if the concentration of iron in the food exceeds a certain limit value, somewhere between 0.71 and 1.23%. With iron in the food below this value, cyclic starvation-feeding markedly potentiates accumulation of iron in the liver in the course of several months, but siderosis is moderate. With iron in the food above the limit value, cyclic starvation-feeding and feeding ad libitum can equally lead to massive siderosis of the liver.
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PMID:Effects of cyclic starvation-feeding and of splenectomy on the development of hemosiderosis in rat livers. 481 98

An elevated plasma glucagon concentration and reduced T3 production from T4 have both been observed in several clinical disorders, including hepatic cirrhosis, uremia, diabetes mellitus, and starvation. The question of whether glucagon has a direct effect on T3 production was studied in normal rats infused iv with [125I]T4 of [125I]T3 and 3 micrograms T4/day, using implanted minipumps. The blood [125I]T4 and [125I]T3 levels maintained a plateau between the fifth and ninth days of infusion. Each animal also received a second minipump, implanted ip, that infused either a diluant solution or 30 micrograms glucagon/100 g BW . day. After 7 days of continuous infusion, the glucagon-treated animals showed a 20% increase in plasma glucose and a 4-fold increase in plasma glucagon from baseline. However, the levels of insulin, T4, and T3 remained unchanged. The MCRs and the disposal rates of T4 and T3, calculated by the constant infusion method, showed T4 and T3 MCRs to be 0.99 +/- 0.18 and 11.25 +/- 2.52 ml/h . 100 g, respectively, and T4 and T3 disposal rates to be 68 +/- 10 and 9 +/- 2 ng/h . 100 g; there was no difference between the control animals and the glucagon-infused animals. T3 production was also determined in vitro from T4 added to a liver homogenate. Compared to control animals, the liver homogenate prepared from glucagon-infused animals showed a modestly higher T3 production rate throughout the 60-min incubation period (P = 0.025--0.05). However, the concentration of nonprotein-bound sulfhydryls was similar in the liver, kidney, brain, muscle, and heart of the two animal groups. In conclusion, glucagon does not have an important regulating role on the peripheral metabolism of thyroid hormone and T3 production in rats.
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PMID:Comparison of peripheral thyroid hormone metabolism in normal rats and in rats receiving prolonged glucagon infusion. 704 21


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