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)

Plasma immunoreactive glucagon (IRG) was examined in volunteers with biopsy-proven cirrhosis of the liver after recovery from surgical portal--caval anastomosis. A wide range of increased total plasma IRG concentrations was found after overnight fast in groups of cirrhotic subjects with and without fasting hyperglycemia. Gel filtration chromatography of plasma showed a major component in the 3500-mol wt fraction in all cases so studied. Administration of glucose i.v. caused rapid suppression of total plasma IRG in normoglycemic and non-insulin-dependent hyperglycemic cirrhotic subjects. After administration of oral glucose, total plasma IRG was suppressed rapidly in normoglycemic cirrhotic subjects, while non-insulin-dependent hyperglycemic cirrhotic subjects exhibited delayed but prolonged suppression. Chromatography of selected plasma with glucose-suppressed total IRG showed a major decrease in the 3500-mol wt component in every case. Exaggerated increments of plasma gastric inhibitory polypeptide were demonstrable in both groups of cirrhotic individuals after administration of oral glucose, and it is speculated that this peptide may contribute to stimulation of glucagon secretion in liver disease associated with insulin deficiency.
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PMID:Hyperglucagonemia in liver cirrhosis with portal-systemic venous anastomoses: responses of plasma glucagon and gastric inhibitory polypeptide to oral or intravenous glucose in cirrhotics with normal or elevated fasting plasma glucose levels. 44 82

Five nonalcoholic diabetic women were clinically and histologically verified as having micronodular cirrhosis. In this series all the patients were over 50 years of age, and showed obesity, hyperglycemia, enlarged liver and mild abnormalities of liver function tests. The histological findings differed from hepatitic cirrhosis. In two patients serial biopsies confirmed development of cirrhosis from centrilobular necrosis.
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PMID:Five patients with nonalcoholic diabetic cirrhosis. 46 92

Arteriosclerotic and nonarteriosclerotic rats were treated with carbon tetrachloride (CCL4) to induce cirrhosis of the liver. Massive myocardial infarction was then induced in intact and CCL4-treated animals. During acute necrosis (Days 1 thru 3), animals were killed at 4, 8, 12 and 24 h on Days 1 and 2, and during myocardial repair on Days 4, 5 and 8. During the induction of cirrhosis, animals developed polydypsia, polyuria, and hyperglycemia; during myocardial infarction, the arteriosclerotic + cirrhotic animals developed severe and persistent congestive heart failure, i.e., hydrothorax. Adrenal and thymus gland weights and corticosterone levels indicated that cirrhosis per se increased pituitary--adrenal activity, particularly in arteriosclerotic animals. Enzyme levels of SGOT and SGPT demonstrated severe hepatic damage due to cirrhosis and acute myocardial infarction. Blood triglycerides and cholesterol responded abnormally in cirrhotic animals during acute myocardial ischemia due to their entrapment within hepatic cells. The cirrhotic animals manifested poor myocardial repair with persistent foci of necrosis, calcification, and a high incidence of large, occlusive, atrial thrombi. It is suggested that cirrhosis interferes with lipid metabolism and adrenal steroid conjugation leading to abnormal levels of mineralocorticoids which favor congestive heart failure, poor myocardial repair, and atrial thrombosis.
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PMID:Effect of CCL4-induced cirrhosis on the pathophysiologic course of acute myocardial infarction in nonarteriosclerotic vs arteriosclerotic male rats. 46 16

In animals, the effects of vasoactive intestinal polypeptide (VIP) include peripheral vasodilation, hyperdynamic circulation, hyperglycemia, and hyperventilation. Because these phenomena are noted in patients with cirrhosis, it has been postulated that VIP might be escaping hepatic inactivation and entering the systemic circulatory system and contributing to these abnormalities. The major purpose of this study is to establish whether or not VIP levels are elevated in patients with cirrhosis. Additional goals are to determine if VIP levels are elevated in acute liver disease and in chronic illnesses with secondary liver involvement. The data demonstrate that patients with cirrhosis and those with acute liver disease or chronic illnesses with secondary hepatic involvement have a wide range of VIP levels with mean values significantly above that of normal individuals and patients with chronic illness and no liver involvement.
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PMID:Circulating levels of vasoactive intestinal polypeptide in liver disease. 47 38

It is evident that ethanol by itself or one of its metabolites produces alterations in transport, metabolism and disposition of carbohydrates. Ethanol acts via changes in the redox state of co-factors; e.g. ethanol-induced hypoglycemia is due, partly, to the inhibition of hepatic gluconeogenesis by ethanol as a consequence of the increased NADH2/NAD ratio in patients whose glycogen stores are already depleted. On the other hand, hyperglycemia has also been described in patients with alcoholism. Although its mechanism is still obscure, abnormal hormonal secretion of insulin, catecholamines and glucocorticoids has been incriminated. Finally, structural changes of the liver and pancreas such as cirrhosis and pancreatitis produced by chronic alcohol consumption should also be considered as pathogenetic factors in a variety of clinical states involving deranged carbohydrate metabolism.
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PMID:Alcohol induced changes of carbohydrate metabolism [author's transl]. 70 66

Glucagon is secreted not only by A2-cells of the pancreatic islets but also by A cells in the gastric fundus and duodenum. Several reports have demonstrated that the glucagon plasma concentration is increased in genetic diabetes as well as in many conditions associated with a decreased glucose tolerance such as hepatic cirrhosis, myocardial infarction, infectious diseases, burns, taumatic shock, glucagonomas, acute pancreatitis, acromegaly, pheochromacytoma and Cushing's syndrome. Hyperglucagonemia is particularly important in diabetic ketoacidosis and in non-ketotic hyperosmolar coma. The mechanisms responsible for the diabetic's hyperglucagonemia remain controversial. According to several authors, the increased glucagon secretion is, for its main part, secondary to a prolonged defect in insulin secretion and thus relatively insensitive to an acute insulin administration. According to others, the A cell abnormality is of primary origin, independant from insulin deficiency and its effects are cumulative with those of the insulin lack. Several reports dealing with induced or spontaneous experimental diabetes are in favor of the first or the second hypothesis. It appears likely that glucagon plays a role in the metabolic derangments of diabetes. Indeed, hepatic glucose production is closely related to the ratio of molar concentrations of insulin and glucagon. Finally, in insulin-dependant diabetics, somatostatin infusion reduces plasma glucagon concentration and blood glucose and prevents the development of ketosis after withdrawal of insulin therapy. These results illustrate the contribution of glucagon in the pathogenesis of hyperglycemia and ketosis. Several arguments have been accumulated in favor of the following concept: diabetes hyperglycemia results both from glucose under-utilization secondary to insulin lack and from hepatic glucose over-production due to glucagon excess. Although controversial, the role of glucagon in ketogenesis appears likely.
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PMID:[The role of glucagon in hyperglycemia. A review (author's transl)]. 79 28

Insulin-induced glucose metabolism was investigated in 26 patients with biopsy-proven liver cirrhosis and 10 control subjects. Two glucose clamp protocols together with continuous indirect calorimetry were performed to examine whether reduced rates of glucose oxidation and/or nonoxidative glucose metabolism explain insulin resistance in liver cirrhosis. Using a 4-hour, two-step protocol (0-2 hours, plasma glucose 5.2 mmol/L, plasma insulin 92 mU/L to test the half-maximum response; 2-4 hours, hyperglycemia 10.0 mmol/L, plasma insulin 442 mU/L to test the maximum cellular glucose disposal) liver cirrhosis reduced glucose disposal to 45% and 60% of control values, respectively. Simultaneously, insulin-induced increases in glucose oxidation, plasma lactate levels, and lipogenesis were normal, whereas nonoxidative glucose metabolism was reduced (-82% and -47% of controls, respectively). To determine whether reduced nonoxidative glucose metabolism was caused by reduced glucose disposal, glucose disposal was "matched" to normal values in a subgroup of cirrhotic patients. Nonoxidative glucose metabolism values were normal, but plasma lactate concentrations disproportionally increased (+96%) after "matching" glucose disposal. Insulin resistance was independent of the etiology of the cirrhosis, the biochemical parameters of parenchymal cell damage and liver function, and the clinical and nutritional state of the patients. It is concluded that liver cirrhosis impairs insulin sensitivity and maximum cellular glucose disposal. Reduced glucose disposal is caused by defective glucose storage. Insulin resistance is independent of the etiology of liver cirrhosis and of the clinical and nutritional state of the patient.
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PMID:Mechanism of insulin resistance associated with liver cirrhosis. 158 21

To study the consequences of hyperglycemia on glucose and nitrogen metabolism in cirrhosis, an hyperglycemic clamp was performed in 5 cirrhotic patients and 5 normal controls during two subsequent periods of 90 min, at 7.78 and then at 13.89 mmol/l. In the first period, glucose infusion and metabolic clearance rates were decreased in cirrhotics vs controls (p less than 0.05). In the second period, this difference between the two groups disappeared because of a more important enhancement in cirrhotics. Baseline plasma C peptide levels and those during hyperglycemia were the same during hyperglycemia in both groups, but plasma insulin level rose more in cirrhotics (p less than 0.05). Baseline insulin secretion following IV glucagon was reduced in cirrhotics vs controls (p less than 0.05), but became normal in the hyperglycemic state. Plasma glucagon levels were enhanced at all times in cirrhotics vs controls (p less than 0.01), but dropped more in cirrhotics vs controls (p less than 0.05). Insulin responsiveness, defined as the "glucose consumption: plasma insulin concentration" ratio was reduced in cirrhotics at 7.78 mmol/l (p less than 0.01), but was the same in both groups at 13.80 mmol/l because of a more important enhancement in cirrhotics, reflecting an improvement of insulin action probably at the post-receptor level and of non-insulin-mediated glucose transport. Hyperglycemia induced a drop in plasma concentration and muscular release of all aminoacids, excepted alanine, between the basal state and the end of the study. Aminoacid concentration rose only in cirrhotics, without any change in muscular output. In the same time, blood ammonia level rose only in cirrhotics, without reduction of muscular uptake.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Consequences of hyperglycemia on glucose and nitrogen metabolism in liver cirrhosis. A study using a hyperglycemic clamp]. 219 90

Forty-two patients with nonalcoholic steatohepatitis were followed for a median of 4.5 yr (range = 1.5 to 21.5 yr). Except for two patients with lipodystrophy, all were obese; 35 of 42 were women, 26 of 32 were hyperlipidemic and 15 were hyperglycemic. Upper abdominal pain was the most common reason for presentation. Initial liver biopsy specimens showed the presence of macrovesicular fatty infiltration, lobular (acinar) inflammation, apoptosis, Mallory bodies (in four cases) and fibrosis (in 18 cases). Cirrhosis was present at initial diagnosis in one subject and in another two subjects liver biopsy showed marked fibrosis with disturbed architecture. Serial liver biopsy specimens revealed minimal or no apparent progression of the disorder in most of the patients, in keeping with their benign clinical course. However, one patient showed progression from fibrosis to cirrhosis during the 5-yr observation period, and in the patients with extensive fibrosis the liver disease evolved from one of active inflammation to one of inactive cirrhosis without fat or inflammation. The patient with cirrhosis later died of hepatocellular carcinoma. The severity or type of hepatic change did not correlate with the degree of obesity, hyperlipidemia or hyperglycemia. However, in individual patients, poorly controlled diabetes and rapid weight loss preceded the onset of steatohepatitis. We conclude that nonalcoholic steatohepatitis is a cause of hepatic inflammation histologically resembling that of alcohol-induced liver disease but usually slowly progressive and of low-grade severity. However, the disorder may ultimately result in cirrhosis. Nonalcoholic steatohepatitis should be distinguished from alcoholic steatohepatitis and recognized as a further cause of "cryptogenic cirrhosis."
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PMID:The natural history of nonalcoholic steatohepatitis: a follow-up study of forty-two patients for up to 21 years. 1503 Sep 72

In animals, there may exist a hyperemic response in the portal circulation during intravenous administration of hypertonic glucose, but a hemodynamic response of this kind has never been described in man. This study was designed to evaluate if hyperglycemia itself could induce systemic or splanchnic hemodynamic changes in patients with cirrhosis. Sixteen patients with cirrhosis were studied before and during i.v. infusions of hypertonic (900 mOsmoles per liter) glucose (n = 8), mannitol (n = 4) or saline (n = 4) at 2 ml per min. In the group receiving glucose, there were significant increases in hepatic venous pressure gradient (+12%), azygos blood flow (+27%) and pulmonary capillary pressure (+32%), while calf blood flow decreased (-26%). No changes occurred in the mannitol or saline groups. Changes in plasma osmolality, plasma volume, splanchnic oxygen extraction and vasoactive hormones, including vasoactive intestinal polypeptide and glucagon, did not appear to be involved in the mechanism of these vasoactive phenomena. It is suggested that the possible deleterious effects of increase in portal pressure and azygos blood flow should be taken into consideration when administering hypertonic glucose to patients with portal hypertension.
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PMID:Systemic and splanchnic hemodynamic effects of intravenous hypertonic glucose in patients with cirrhosis. 337 82


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