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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is proposed that severe impairment of liver function in cirrhosis or portacaval shunt results in unrestricted entry of insulin into the peripheral circulation. The ensuing high level of insulin promotes excessive removal of the branched-chain aminoacids by muscle, thereby lowering the plasma levels of these aminoacids. In consequence, the competitive action of the branched-chain aminoacids on the entry of tryptophan into the brain is reduced, more tryptophan enters the brain, and serotonin is synthesised in excess, thus facilitating hepatic coma.
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PMID:Insulin, plasma aminoacid imbalance, and hepatic coma. 4 85

The breakdown of proinsulin in the pancreatic beta cell yields insulin and C-peptide which are secreted in equimolar amounts. Unlike insulin, C-peptide is not degraded significantly by the liver, so that its measurement should give a better assessment of insulin secretion than estimation of peripheral insulin levels alone; particularly in the presence of hepatic dysfunction. Plasma C-peptide and insulin response to an oral glucose load have therefore been assessed in 14 cirrhotic and 7 normal subjects. Cirrhotic patients were divided into hyperinsulinaemic and normoinsulinaemic groups based on fasting plasma-insulin concentrations. Fasting blood-blucose and plasma-C-peptide concentrations were the same in normal and cirrhotic subjects, suggesting that basal pancreatic insulin secretion was the same in all subjects. Thus the C-peptide/insulin ratio was significantly decreased in hyperinsulinaemic subjects (2-13 +/- 0-31, compared with 4-63 +/- 0-48 in controls). After oral glucose, the two groups of cirrhotic patients showed the same glucose intolerance. C-peptide concentrations were also the same but insulin concentrations were markedly increased in the hyperinsulinaemic group. It is suggested that pancreatic insulin secretion is not increased in cirrhosis and that the peripheral hyperinsulinism is due solely to decreased hepatic insulin degradation secondary to either spontaneous portal-systemic shunting or to parenchymal damage.
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PMID:Hyperinsulinism of hepatic cirrhosis: Diminished degradation or hypersecretion? 6 54

The female patient initially showed the acquired type of total lipoatrophy at about 8 years of age. At 12 years of age, the onset of diabetes mellitus was speculated from advanced pyodermia and dedentition. At 29 years of age, glucosuria was found, and she developed proteinuria, ascites, and pretibial edema. The physical examination revealed: hepatosplenomegaly, complete absence of subcutanous fat, cutaneous xanthomas, and emaciated facies with pronounced zygomatic arches. Diabetic retinopathy was revealed in the ophthalmological examination, and nephropathy was evident in renal biopsy specimens. She also had peripheral diabetic neuropathy. No adipose tissue was found in the mesenterium under peritoneoscopy. The hepatic biopsy specimen revealed advanced portal liver cirrhosis. Laboratory findings included: hyperlipidemia, elevation of BMR without evidence of hyperthyroidism, impaired renal function, and undetected anti-insulin antibodies and anti-insulin antibodies. Endocrinological examinations revealed normal value, except for an impaired hGH response in the arginine test. C-peptide immunoreactivity was high. Her condition was fairly well controlled by 140 units of insulin injection daily.
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PMID:Lipoatrophic diabetes. Report of a case. 15 92

Glucagon was tested for its effect on plasma adenosine 3',5'-cyclic monophosphate (cyclic AMP), insulin, and glucose in healthy subjects and in patients with advanced cirrhosis of the liver. In the normal subjects, intravenous infusion of glucagon caused a significant increase in plasma cyclic AMP, glucose, and insulin. In advanced cirrhotics, plasma cyclic AMP, glucose, and insulin did not increase. Adenylate cyclase concentration was measured in liver tissue from end stage cirrhotic patients and from brain-dead organ donors whose cardiovascular function was maintained in a stable state. Basal and total adenylate cyclase concentration were not different in the two groups. Adenylate cyclase from the livers of advanced cirrhotics was, however, significantly less responsive to glucagon stimulation than was that from donor livers. Hepatocytes in advanced cirrhosis have abnormal metabolic behavior characterized by abnormal adenylate cyclase-cyclic AMP response to hormonal stimulation.
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PMID:Cyclic AMP metabolism and adenylate cyclase concentration in patients with advanced hepatic cirrhosis. 21 45

A simple diagnostic strategy in the diagnosis of insulinoma in adult subjects is proposed based upon the literature and own experiences. It comprises measurement of plasma proinsulin, insulin and C-peptide as well as blood glucose after an overnight fast. When a low or normal proinsulin concentration is found, organic hyperinsulinaemia is very unlikely, while elevated proinsulin, after exclusion of uremia, hepatic cirrhosis, thyreotoxicosis and surreptitious administration of insulin or sulfonylurea drugs, strongly indicates this condition.
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PMID:Strategy in the diagnosis of insulinoma. 22 87

In view of the importance of insulin in hepatic cell proliferation and regeneration, disturbances might be expected in these processes in diabetics. The relative importnace of insulin replacement given intraportally rather than subcutaneously is discussed. Results are presented showing that even when normoglycaemia is achieved with peripheral insulin infusion using the 'artificial pancreas' there are still abnormalities in intermediary metabolism. The incidence of cirrhosis in diabetes is reviewed and it is concluded that the evidence is poor for an increase in diabetics. Finally it is shown that in the normal diabetic rat changes are observed after partial hepatectomy consistent with an increase in redox potential within the regenerating liver. Insulin treatment improves redox status but does not completely reverse the changes shown.
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PMID:Hepatotrophic factors: implications for diabetes mellitus. 24 6

To investigate the development of diabetes mellitus in patients with thalassemia major, plasma glucose and immunoreactive insulin (IRI) levels following oral glucose and intravenous tolbutamide and glucose disappearance rates following intravenous insulin were measured in 10 patients before and during five years on a high transfusion program (HTP). Plasma immunoreactive glucagon (IRG) levels following oral glucose, intravenous insulin, and arginine were measured during the sixth year. Serial percutaneous liver biopsies were performed on seven patients. The oral glucose tolerance tests (OGAT) and mean peak IRI levels were normal in nine of 10 patients before HTP. After HTP was begun a progressive deterioration of OGTT occurred despite normal IRI levels. Following tolbutamide, the mean per cent fall in plasma glucose in the patients before HTP was significantly less than in controls (p less than 0.01) and similar to that of controls during five years of HTP in spite of higher than normal peak IRI levels. Of seven survivors after six years of HTP, three had normal OGTT and four had chemical diabetes; mean peak IRI levels were normal, but fasting IRG levels were significantly higher than in controls (p less than 0.05). In all seven patients, plasma IRG failed to increase following insulin-induced hypoglycemia and was significantly higher than in controls after arginine (p less than 0.01); after oral glucose, plasma IRG fell significantly below that of fasting only in the patients with chemical diabetes (p less than 0.03). Following intravenous insulin, the mean per cent fall in glucose before and during HTP was significantly less than in controls (p less than 0.01). Hemosiderosis and cirrhosis were present in all biopsied patients. Four patients died; two had chemical and two had nonketotic insulin-dependent diabetes. These data suggest that diabetes mellitus occurs frequently in patients with thalassemia on HTP and that insulin resistance and hyperglucagonemia, possibly due to cirrhosis, are important etiologic factors.
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PMID:Carbohydrate metabolism and pancreatic islet-cell function in thalassemia major. 32 76

In order to explain the increase of total IRI frequently observed at basal status, and after glucose administration, in patients with chronic liver disease, plasma proinsulin-like component and insulin levels have been studied in fourteen patients with liver cirrhosis associated or not with clinical or subclinical diabetes mellitus. A significative increase of plasma insulin was observed at basal status and after a glucose load not only in subjects with clinical or subclinical diabetes but also in those patients without carbohydrate abnormalities. This increase is apparently not correlated to any clinical characteristic and is associated in fasting and after glucose load with increased proinsulin-like component levels especially in patients with clinical or subclinical diabetes.
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PMID:Plasma proinsulin-like components and insulin in chronic liver disease. 32 82

To clarify further the etiology of the carbohydrate intolerance in idiopathic hemochromatosis, we investigated the glucose, insulin, C-peptide, and glucagon responses to arginine (0.5 g/kg) infused during 30 min in lean normal subjects; in insulin-requiring subjects with hemochromatosis, genetic diabetes, and total pancreatectomy; and in nondiabetic cirrhotic subjects without portosystemic shunting. Serum insulin, C-peptide, and glucagon responses (30K antibody) were determined by RIA, and glucose level was determined by a glucose oxidase technique. Hemochromatotic and genetic diabetic subjects had similar basal glucose (157 +/- 25 vs. 168 +/- 40 mg/dl) and C-peptide (0.73 +/- 0.42 vs. 0.65 +/- 0.22 ng/ml) values, with subnormal C-peptide peak responses to stimulation (1.05 +/- 0.38 and 1.40 +/- 0.83 vs. 3.95 +/- 0.4 ng/ml in normals; P less than 0.05). No glucagon or C-peptide response to arginine was seen in any pancreatectomized subject. Similar but excessive glucagon levels were present in hemochromatosis, diabetes, and cirrhosis under basal conditions (166 +/- 24, 232 +/- 111, and 263 +/- 116 vs. 76 +/- 15 pg/ml; P less than 0.05) and after arginine stimulation (782 +/- 80, 834 +/- 123, and 902 +/- 275 vs. 489 +/- 81 pg/ml; P less than 0.05) when compared with normals. The excessive glucagon levels found in hemochromatosis, diabetes mellitus, and cirrhosis contrast to the absent response in pancreatectomized subjects and indicate that generalized islet cell destruction is not the major factor in diabetic hemochromatotic subjects.
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PMID:Pancreatic alpha-cell function in diabetic hemochromatotic subjects. 38 22

Increased glucagon (IRG) levels have been documented in liver cirrhosis, particularly associated with portal-systemic shunting. In spite of increased insulin (IRI) levels, IRI/IRG are reduced. This alteration has been proposed to have a pathogenic role in plasma aminoacid imbalance which seems to account for hepatic encephalopathy. We studied IRG and IRI/IRG in 13 controls and in 3 groups of cirrhotics, divided on the basis of their mental state. Glucagon was determined by means of 30 K Unger's antibody; insulin by a double antibody technique. Results are expressed in the table as means +/- SEM. (Formula: see text)A progressive increase in IRG secretion is present in cirrhotics and correlates with the mental state; IRI/IRG is not altered in cirrhosis until neurological distrubances are present. A relative fall in IRI which can no more balance the increasing IRG values characterizes hepatic encephalopathy.
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PMID:The role of insulin and glucagon in the plasma aminoacid imbalance of chronic hepatic encephalopathy. 38 61


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