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

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

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 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

An intact pituitary gland capable of secreting growth hormone has long been considered the prime requirement for the achievement of skeletal growth potential in man. Recent studies have revealed that the growth-promoting action of growth hormone is an in-vivo phenomenon which cannot be mimicked by the addition of the hormone to skeletal tissue in vitro. The humoral agent responsible for skeletal growth has now been identified as somatomedin, a peptide produced in the liver under the stimulus of pituitary growth hormone. Serum levels of somatomedin are measured in a bioassay system by monitoring the stimulation of uptake of labelled sulphate by cartilage. Low levels of somatomedin activity are detected in the serum of children with growth hormone deficiency and short stature; the levels are high in acromegalics and low in patients with cirrhosis of the liver or chronic renal failure. Undernourished children also have low levels despite reaised serum levels of growth hormone; this suggests the presence of an inhibitor which lowers the growth-promoting activity of the somatomedin molecule. Adequate nutrition in these children results in the restoration of serum somatomedin levels to normal. Attempts to isolate and purify somatomedin have led to the identification of a group of substances sharing similar actions on skeletal tissue. Insulin has also been demonstrated to share some of these growth-promoting activities but varies in its organ specificity. Nerve growth factor, epidermal growth factor and proinsulin are other molecules which form a large group of growth promoting peptides which may all be related to the somatomedins.
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PMID:Somatomedins. 115 75

A radioimmunoassay using a proinsulin-specific antiserum that does not react preferentially with the split forms of proinsulin has been used to compare the response of circulating proinsulin to low (25 g) and high (75 g) oral glucose loads in healthy subjects and in patients with liver cirrhosis. The patients were divided into two groups: Group A (n = 7) with normal glucose tolerance and Group B with diabetic (n = 5) and impaired (n = 1) glucose tolerance. There was no apparent correlation between glucose tolerance and the results of quantitative liver function tests. In the fasted state, the concentrations of serum proinsulin did not differ significantly in patients of Group A (0.022 +/- 0.002 nmol/l) or Group B (0.026 +/- 0.004 nmol/l) from those in healthy subjects (0.021 +/- 0.002 nmol/l). After 75 g glucose, the rise in serum proinsulin to a maximum concentration of 0.082 +/- 0.012 nmol/l in patients of Group A and to 0.070 +/- 0.019 nmol/l in Group B was not significantly different at any time point up to 180 min from the rise in healthy subjects (to 0.063 +/- 0.005 nmol/l). After 25 g glucose, the response of serum proinsulin in Group B patients (maximum concentration 0.035 +/- 0.003 nmol/l) was not significantly different from that in healthy subjects (maximum concentration 0.032 +/- 0.003 nmol/l) but a slightly enhanced release was observed in the Group A patients (maximum concentration 0.049 +/- 0.003 nmol/l) that was significantly greater (P less than 0.05) at 60 min post-glucose. In contrast, the concentrations of serum immunoreactive insulin and immunoreactive C-peptide in all patients with cirrhosis were significantly elevated compared with healthy subjects both in the fasted state and at several time points following high and low oral glucose. In the fasted state, the serum proinsulin/C-peptide molar ratio, an index of the relative state of secretion of proinsulin and insulin, was significantly lower (P less than 0.05) in both groups of cirrhotic patients than in healthy subjects. After high and low glucose, this ratio fell in all patients and in the healthy subjects. We conclude that cirrhosis of the liver is associated with a hypersecretion of insulin but hyperproinsulinaemia does not contribute appreciably to the elevated concentration of immunoreactive insulin in the peripheral circulation.
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PMID:Hypersecretion of proinsulin does not explain the hyperinsulinaemia of patients with liver cirrhosis. 330 24

Plasma concentrations of insulin, C-peptide, and proinsulin were measured in different vascular beds in order to determine renal, hepatic, and systemic kinetics of the endogenous peptides in the fasting condition. Nineteen nondiabetic subjects were studied, two were normal, nine had minor vascular disorders, four had cirrhosis without organic kidney disease, and four had organic kidney disease with moderately decreased glomerular filtration rate. In subjects without organic kidney disease the arteriorenal venous extraction ratios of insulin, C-peptide, and proinsulin were mean 0.27, 0.20, and 0.21, respectively (n = 14). These values were significantly reduced in kidneys with organic disease. Renal plasma clearance values of insulin, C-peptide, and proinsulin were mean 113, 87, and 90 mL/min, respectively (n = 6). Urinary clearances were substantially lower (0.8, 13, 3.5 mL/min, respectively), indicating that a significant degradation of these peptides also takes place in the normal kidney. In subjects without liver disease the estimated hepatic extraction ratio of insulin was mean 0.48, under the assumption that no C-peptide is removed by the liver. Endogenously released insulin was removed from plasma in kidney, liver, and elsewhere in the approximate proportion 10%:65%:25%, whereas, C-peptide was removed by one half in kidney and the other half elsewhere. The overall metabolic clearance rates of insulin and C-peptide were estimated to be 15 and 4.5 mL/min/kg, respectively. The results indicate that the kidney contributes substantially to removal of insulin, C-peptide, an proinsulin, mainly by degradation, less by urinary excretion.
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PMID:Kinetics of circulating endogenous insulin, C-peptide, and proinsulin in fasting nondiabetic man. 355 49

The levels of proinsulin, immunoreactive insulin, true insulin (calculated from the difference, namely immunoreactive insulin-proinsulin) and C-peptide were determined in the fasting state and during a 3-h oral glucose tolerance test after administration of 100 g of glucose in 12 patients with cirrhosis with normal oral glucose tolerance test (50 g) and in 12 healthy subjects serving as controls. In the patients with cirrhosis the serum levels of proinsulin and immunoreactive insulin were significantly higher in the fasting state and after glucose loading than in the healthy subjects. The serum level of true insulin was also higher in the patients with cirrhosis, but the difference was less pronounced and only significant at a few of the time points. The serum level of C-peptide was very similar in both groups. These results emphasize that cirrhosis is a condition in which the serum proinsulin level is raised and that this hyperproinsulinaemia contributes greatly to the increased immunoreactive insulin levels observed in patients with this disease.
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PMID:Serum levels of true insulin, C-peptide and proinsulin in peripheral blood of patients with cirrhosis. 636 78

Proinsulin, insulin and C-peptide levels were investigated in chronic renal, hepatic and muscular disorders. The proinsulin levels in human plasma were determined by radioimmunoassay using insulin-degrading enzyme (IDE). The fasting levels of proinsulin in 29 patients with chronic renal failure (0.95 +/- 0.05) were significantly higher than those in 10 patients with liver cirrhosis (0.46 +/- 0.04), six with muscular dystrophy (0.37 +/- 0.02) and 52 normal subjects (0.24 +/- 0.02 ng/ml, mean +/- S.E.). The fasting levels of insulin and C-peptide in chronic renal failure were also the highest among these groups. The insulin levels in liver cirrhosis and muscular dystrophy were significantly greater than those in normal subjects and increased molar ratios of proinsulin to total insulin immunoreactivity in chronic renal failure were observed. These results suggest that the kidney, liver and muscle are related to circulating insulin levels and that the kidney plays a particularly important role in circulating proinsulin levels. It can be concluded that increases in these peptides are due to a hypersecretion of B-cells, a decreased degradation or excretion.
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PMID:Plasma levels of proinsulin, insulin and C-peptide in chronic renal, hepatic and muscular disorders. 637 42

We used specific, monoclonal antibody-based, two-site immunoradiometric assays to test the hypothesis that serum levels of proinsulin and des-31,32 proinsulin would be increased in cirrhosis, particularly in those with overt diabetes. A 75-g oral glucose tolerance test was performed after an overnight fast in eight cirrhotic patients with diabetes (fasting blood glucose, 7.8 +/- 2.2 [SE] mmol/L), seven nondiabetic cirrhotic patients, and eight normal control subjects. Fasting serum immunoreactive insulin levels were approximately six times higher in cirrhotics than in controls, but were not different between diabetic and nondiabetic cirrhotic patients. After oral glucose, the incremental area under the serum insulin concentration curve was 3,475 +/- 1,009 pmol.L-1.h in nondiabetic cirrhotic patients, significantly higher than in controls (761 +/- 48, P < .001) or diabetic cirrhotic patients (881 +/- 186, P < .05). Fasting serum proinsulin levels in diabetic cirrhotic patients (24.0 +/- 5.7 pmol/L) were higher than in controls (2.3 +/- .05, P < .001) or nondiabetic cirrhotic patients (4.4 +/- 0.8, P < .005). Fasting serum levels of des-31,32 proinsulin were also much higher in diabetic cirrhotic patients than in nondiabetic cirrhotic patients or controls (P < .02 and P < .005, respectively). Fasting proinsulin plus des-31,32 proinsulin constituted 12.5% +/- 1.4% of serum immunoreactive insulin in diabetic cirrhotics, higher than in nondiabetic cirrhotics (3.7% +/- 0.5%, P < .001) and normal controls (7.8% +/- 1.5%, P = .035).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The contribution of proinsulin and des-31,32 proinsulin to the hyperinsulinemia of diabetic and nondiabetic cirrhotic patients. 786 24

Glucose intolerance is a common consequence of transfusion therapy in patients with thalassemia major (TM), but the relative contribution of pancreatic damage and insulin resistance to glucose intolerance is unclear. We have investigated oral (OGTT) and intravenous (IVGTT) glucose tolerance, insulin sensitivity, and fasting concentrations of insulin, proinsulin, and des 31,32 proinsulin in 12 patients with TM (seven hepatitis C virus [HCV] antibody-negative and five-positive), eight patients with hepatic cirrhosis, and nine healthy controls. Two-hour plasma glucose concentrations were marginally higher in anti-HCV-negative (median, 7.4 mmol/ L; range, 4.0 to 8.2) and significantly so in anti-HCV-positive thalassemics (median, 8.5 mmol/L; range, 6.4 to to 23.0) and cirrhotics (median, 8.0 mmol/L; range, 4.7 to 17.6) than in controls (median, 5.5 mmol/L; range, 3.0 to 6.3). Insulin sensitivity was also reduced in the three patient groups (P < .05). Insulin resistance was the main determinant of oral glucose intolerance in all patient groups (partial r2 = .49, P < .0001, n = 28). In turn, the main determinants of insulin insensitivity in TM patients were liver damage (albumin, r = .67, P = .02) and serum ferritin concentration (r = -.62, P = .03). There was no relationship of either 2-hour or incremental insulin concentrations with ferritin levels or with HCV status in TM subjects. Moreover, these patients showed no elevation of concentrations of proinsulin and des 31,32 proinsulin, markers of pancreatic beta-cell damage, in excess of those observed in cirrhotic patients. In conclusion, the glucose intolerance of TM, like that of cirrhosis, is associated with insulin resistance, not insulin deficiency, and may be a direct or indirect consequence of hepatic damage.
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PMID:Glucose intolerance in thalassemia major is related to insulin resistance and hepatic dysfunction. 862 11


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