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)

The aim of this investigation was to determine the total concentrations of the insulin-like growth factors (IGF-I and IGF-II) in the blood serum of patients with liver cirrhosis and to evaluate their association with the condition. Cirrhosis was alcohol induced (n=27), of viral origin (n=17) or due to combined or other causes (n=21) and was moderate or severe in similar numbers of cases (Child A: n=21; Child B: n=21; Child C: n=23). While serum levels of both peptides were lower in patients than in age-matched healthy subjects (n=81), there was considerable overlap into the lower normal range for IGF-I. Moreover, no correlation between disease severity (Child score) and serum IGF-I was observed. Since a total of 78% of the results for IGF-II were outside the normal range (95% confidence interval) and serum concentrations were correlated with Child score (P=0.007), it is suggested that serum IGF-II concentrations may reflect compromised hepatic function more closely than IGF-I.
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PMID:Serum insulin-like growth factor (IGF)-II is more closely associated with liver dysfunction than is IGF-I in patients with cirrhosis. 1072 82

IGF-I is an anabolic hormone which has been reported to increase bone formation in several conditions of undernutrition. Advanced liver cirrhosis is associated with osteopenia and also with low serum levels of IGF-I. Previous results showed that low doses of IGF-I increase osteoblastic activity and decrease bone reabsorption in early liver cirrhosis. The aim of this study was to evaluate whether IGF-I-treatment also induces beneficial effect on osteopenia associated with advanced cirrhosis. Rats with ascitic cirrhosis were divided into two groups: group CI (n=10) which received saline and group CI+IGF (n=10) which were treated with IGF-I (2 microg/100 g bw x day, sc, during 21 days). Healthy controls which received saline were studied in parallel (CO n=10). On the 22nd day, the animals were sacrificed, and bone parameters were analyzed in femur. Posterior-anterior diameter was similar in all groups. No significant differences were observed in bone content of calcium, total proteins, collagen and hydroxyapatite in cirrhotic rats as compared with controls. However, CI rats showed significant reductions in total bone density (-13.5%, p<0.001) assessed by densitometry and radiological study. In CI+IGF rat bone density (assessed by densitometry) improved significantly as compared with CI animals. In summary, osteopenia characterized by loss of bone mass and preserved bone composition was found in rats with advanced cirrhosis induced by CCl4 and phenobarbital in drinking water. This bone disorder is partially restored by treatment with low doses of IGF-I during only three weeks. Thus, IGF-I could be considered as a possible therapy for osteopenia associated with advanced liver cirrhosis.
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PMID:Effects of IGF-I treatment on osteopenia in rats with advanced liver cirrhosis. 1101 14

The protein synthetic activity of the liver is diminished in cirrhosis. The aim of this study was to investigate possible changes in the serum IGF-IGFBP system among patients with alcoholic liver cirrhosis (ALC). The results obtained demonstrated that serum IGF-I and IGF-II concentrations were significantly lower in patients with ALC than in healthy persons (P=0.0008 for IGF-I and 0.0002 for IGF-II). The IGFBP profile was markedly altered and the 34 kDa IGFBP from patients had higher affinity towards 125I-IGF-II compared to the 34 kDa IGFBP of control individuals. Moreover, the 40-45 kDa IGFBP (in isolated complex with 125I-IGF-II) exhibited diminished interaction with concanavalin A, wheat germ, and breadfruit lectins. Modification of the glyco-component of the 40-45 kDa IGFBP seems to be an early event in ALC since change in reactivity towards lectins was noticed in patients with ALC classified as Child score A, whose serum IGF-I and IGF-II levels were within reference limits (the existence of carbohydrate microheterogeneity of this IGFBP was also assessed by lectin-affinity electrophoresis). It is possible that these biochemical alterations may affect the functional activity of the IGFs by changing the dynamics and distribution of these growth factors in the organism.
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PMID:Alterations of IGF-binding proteins in patients with alcoholic liver cirrhosis. 1109 Oct 25

IGF-I stimulates protein synthesis, lowers blood glucose, and affects cell differentiation. The main production site of IGF-I is the liver. One of its binding proteins, IGFBP-1, is also produced by the liver. It is well known that ethanol affects the function of the human liver. Long-term alcohol abuse may therefore not only cause considerable IGF-I and IGFBP-1 production changes, but also changes in IGF-I bioavailability, which at least in part is determined by the IGF-I/IGFBP-1 ratio. Not much is known about how the bioavailability of IGF-I is changed in alcohol abusers. Therefore, the objective of this investigation was to study that matter, and to elucidate how abstinence affects IGF-I bioavailability in man. Three study groups were formed: group N including normal non-addicted subjects, group E ethanol abusers without gross liver insufficiency, and group C alcohol abusers with liver cirrhosis and ascites. Serum concentrations of insulin, GH, IGF-1, and IGFBP-1 were determined in the morning in all participants, and the IGF-I/IGFBP-1 ratios were calculated. These values were compared in the three study groups. In group E comparison was also made between values recorded in the ethanol intoxicated and in the detoxicated states. Patients in group C had low IGF-I levels, high IGFBP-1 levels, and low IGF-I bioavailability as reflected by the IGF-I/IGFBP-1 ratios, which were several-fold reduced compared with subjects in group N (0.6+/-0.2 vs 10.2+/-2.3; p<0.001). Patients in group E had also a low IGF-I/IGFBP-1 ratio in the acute ethanol intoxicated state, which increased after detoxication (from 1.5+/-0.4 to 5.6+/-1.2; p<0.01). It is concluded that alcohol abuse lowers the hepatic production of IGF-I and increases the production of IGFBP-1. This results in a reduced IGF-I bioavailability. However, in patients with not yet clinically apparent liver damage the IGF-I bioavailability increases if the alcohol abuse is stopped. These findings could reflect an important, physiological adaptation, since hypoglycemia may be induced if the blood glucose-lowering power of IGF-I remains strong at a time of ethanol-induced inhibition of the hepatic gluconeogenesis. Chronic alcohol abuse, causing liver cirrhosis, also leads to markedly reduced IGF-I bioavailability, which appears to become permanent, since it prevails more than one week after stopping the alcohol abuse.
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PMID:Decreased IGF-I bioavailability after ethanol abuse in alcoholics: partial restitution after short-term abstinence. 1150 80

To clarify the effects of 1 alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) on bone growth, strength, and turnover in growing rats with liver cirrhosis induced by carbon tetrachloride (CCl(4)) injection, groups of 4-week-old male Wistar rats (n = 10, each) were injected intraperitoneally with CCl(4) twice weekly for 7 weeks. One group was treated with the vehicle alone (Group 1). Three CCl(4)-injected groups were orally administered 1,25(OH)(2)D(3) at doses of 0, 0.05, and 0.1 micro g/kg, respectively (Groups 2, 3, and 4). At the end, serum levels of 1,25(OH)(2)D(3), IGF-I, and osteocalcin were reduced in Group 2 compared to Group 1, and the corresponding values in Group 4 were larger than those in Group 2. Urinary deoxypyridinoline levels increased in Group 2 compared to Group 1, and did not significantly differ in Groups 2-4. The values for bone sizes, mineral content (BMC) in the lumbar vertebra and femur, and ultimate bending load in the femur were reduced in Group 2 compared to Group 1, and lumbar BMC in Group 3 and bone sizes in Group 4 were larger than those in Group 2. The values for lumbar trabecular bone volume in Group 2 were reduced compared to Group 1, and the corresponding values in Group 4 were larger than those in Group 2. Bone formation rates, reduced in Group 2 compared to Group 1, did not differ in Groups 2-4. Parameters for trabecular osteoclasts did not differ among all groups. In the proximal tibia, the value of activation frequency (Ac.f) in Group 2 significantly decreased compared to Group 1. Ac.f values in Groups 3 and 4 were larger than that in Group 2. These data demonstrated that retardation of bone growth in CCl(4)-injected rats was associated with reduced serum 1,25(OH)(2)D(3) and IGF-I levels. The trabecular bone in the rats exhibited low turnover osteopenia. 1,25(OH)(2)D(3) administration partially prevented the growth disturbance, but did not substantially affect bone turnover. Factors other than 1,25(OH)(2)D(3) and IGF-I appeared to be critical in the low turnover osteopenia evident in liver cirrhosis.
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PMID:Effects of 1,25(OH)2D3 on turnover, mineralization, and strength of bone in growing rats with liver cirrhosis induced by administration of carbon tetrachloride. 1266 55

Anorexia nervosa is a syndrome with multifactorial etiology in which several genetic, biologic, psychological and social factors are involved. Patients affected by anorexia nervosa (AN) may develop multiple endocrine abnormalities, e.g. amenorrhea, hypothalamus-pituitary-adrenal axis hyperactivity, low T3 syndrome and peculiar changes of somatotroph axis function. These endocrine abnormalities are also found after prolonged starvation and may represent an adaptive response developed in order to save energy and proteins. It is still a matter of debate whether these endocrine changes are etiologic or secondary. In fact, several evidences suggest the existence in AN of hypothalamus functional alterations, which may be involved in the development and maintenance of the food intake disorder; on the other hand, the increased CRH secretion seems to be secondary to malnutrition as well as GH hypersecretion coupled to low IGF-I levels; the latter is a common finding in AN, as well as in other undernutrition and malabsorption conditions, type 1 diabetes mellitus, liver cirrhosis and catabolic states. Hypothalamic amenorrhea, which is one of the diagnostic criteria for AN, is not linked only to the reduction of body weight but reflects also deep alterations of gonadotropin secretory pattern. Low T3 syndrome is frequently found in AN; on the other hand, an iodide-induced hypothyroidism is quite uncommon. T3 reduction in AN seems to be an adaptive response to prolonged starvation; however the presence of a simultaneous central dysregulation cannot be excluded. Finally, AN patients frequently show defects in urinary concentration or dilution with inappropriate secretion of antidiuretic hormone, which may be due to intrinsic defects in the neurohypophysis or to abnormalities of its regulatory afferent neurons.
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PMID:[Endocrine abnormalities in anorexia nervosa]. 1271 47

Insulin-like growth factors [IGF I and II or somatomedins (SMS)] are polypeptides chemically and biologically correlated with insulin. The main source of synthetic activity and secretion is the liver, although many other tissues have been demonstrated to synthesize SMS. In the circulation, they are not present in a free form, but are mostly bound to a specific carrier protein independently synthesized in the liver. Hepatic or extrahepatic storage organs have not been demonstrated; the half life of the SMS-binding protein complex is between 3 and 4. Synthesis of SMS is regulated by GH, insulin, thyroxine and nutrition (caloric and protein intake, and nitrogen balance). The role of corticosteroids is still a matter of debate: in patients treated with steroids SMS blood levels have been shown to be within normal limits, while biological activity has been demonstrated to be significantly reduced by SMS inhibitors, probably induced by corticosteroid therapy. The biological properties of SMS are related to their structural homology with insulin, and can be summarized as follows: A. Insulin-like activity (glucose oxidation, lipogenesis, glycogen synthesis, inhibition of lipolysis and glycogenolysis); B. Sulphation activity (incorporation of sulphate and leucine into glycosaminglycans of the cartilage); C. Stimulation of fibroblast multiplication; D. Amplification of other hormone activities (GH); E. Complementary anabolic activity with insulin. Low levels of SMS have been demonstrated in hypopituitarism (secondary) or in other diseases independent of GH reduced secretion (primary) such as malnutrition, malabsorption, acute or chronic liver failure and uraemia. Negative nitrogen balance, hypocaloric and/or low protein diets are usually correlated with low levels of SMS. Recently, Schalch et al. reported on the role of orthotopic liver transplantation (OLT) in normalizing SMS blood levels in a group of end-stage liver diseased patients. This preliminary paper deals with changes in IGF-I plasma levels (somatomedin C) in a group of patients affected by end-stage liver cirrhosis before and after OLT.
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PMID:Somatomedin C (IGF I) plasma levels after orthotopic liver transplantation (OLT) in end-stage cirrhotic patients. 1462 70

The malnutrition caused by liver cirrhosis (LC) often worsens the course of the disease. Patients affected by LC often have a low bioavailability of the anabolic liver peptide insulin-like growth factor (IGF)-I. The present study was undertaken to investigate the effect of low doses of IGF-I on the nutritional status and in vivo jejunal transport of D-galactose in anatomically, pathologically and biochemically confirmed moderate, non-ascitic, cirrhotic rats. LC was experimentally induced in growing rats by inhalation of CCl4 and addition of phenobarbital to drinking water. Both the nutritional status, as evaluated by N balance, and in vivo intestinal transport of D-galactose, were significantly impaired in cirrhotic rats. As compared with healthy rats, administration of 20 microg human recombinant IGF-I/kg body weight for 14 d to cirrhotic rats significantly improved N balance variables and restored in vivo intestinal transport of the sugar. However, IGF-I had no effect on the steatorrhoea associated with LC. These results suggest that low doses of IGF-I may have beneficial effects on the malnutrition associated with moderate LC.
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PMID:Effect of insulin-like growth factor-I on nitrogen balance and intestinal galactose transport in rats with moderate liver cirrhosis. 1466 86

GH hypersecretory states include organic and functional causes. Among functional GH hypersecretory states, enhanced somatotroph secretion physiologically occurs at birth associated with reduced IGF-I levels reflecting the still immature sensitivity of liver to circulating GH levels; this may also occur in women exposed to oral extrogens. Pathophysiological conditions of GH hypersecretion are generally associated with congenital or acquired/functional conditions of peripheral GH insensitivity. Genetic alterations of the GH receptor lead to the so called Laron's syndrome. On the other hand, a relevant number of clinical conditions (malnutrition, malabsorption, anorexia nervosa, liver cirrhosis, renal failure, Type 1 diabetes mellitus) are associated with acquired GH insensitivity and a more or less pronounced GH hypersecretion. Both organic and acquired conditions of GH insensitivity show low IGF-I synthesis and release and therefore lack the negative IGF-I feedback action on somatotroph function. GH hypersecretion may be associated with renal failure; however, in this case, the alteration in the metabolic clearance rate of GH would also have a role; moreover, IGF-I levels are generally normal in this condition. Hyperthyroidism is another condition connoted by elevated GH levels that reflects a true GH hypersecretory state and is, in fact, associated with high-normal IGF-I levels; this peculiar condition is likely to be reflecting the stimulatory effect of thyroid hormones on both GH and IGF-I secretion and is promptly reversed by treatment-induced euthyroidism. Apart from these "functional" hypersecretory state, the classic organic GH hypersecretory state is represented by acromegaly or giantism. In these conditions GH hypersecretion is generally sustained by a pituitary adenoma hypersecreting GH alone or together with another pituitary hormone, mostly PRL; less frequently GH hypersecretion may be due to ectopic GHRH hypersection. Exaggerated GH secretion elicits exaggerated IGF-I synthesis and secretion that is, in turn, responsible for the large majority of endocrine signs and symptoms. In the appropriate clinical context of acromegalic features, evidence of concomitant marked GH and IGF-I hypersecretion at baseline demonstrates active acromegaly or giantism and indicates the need for magnetic resonance imaging in order to verify the presence of a pituitary tumor. However, as random measurement of basal GH levels is not reliable for definite diagnosis of acromegaly, it is considered mandatory to rely on the lack of GH suppression below 1 microg/l during oral glucose tolerance test (OGTT) coupled with elevated IGF-I levels. The same criteria are assumed, at present, to define true cure of the disease after (or under) treatment. There is consensus about the assumption that concomitant normalization or persistent abnormality of both OGTT-induced GH nadir and IGF-I levels define a successfully or a poorly controlled disease status, respectively. On the other hand, acromegalic patients with GH nadir above 1 microg/l or IGF-I levels persistently elevated are inadequately controlled and their disease should not be considered inactive. It has been clearly demonstrated that an extended exposure to GH and IGF-I excess level, even if slight, has a very harmful effect on patients; therefore early diagnosis of acromegaly and appropriate definition of its cure are of fundamental extreme in order to plan a prompt and appropriate therapeutic intervention(s) guaranteed also by the continuous improvement in the therapeutic tools available to treat this systemic disease.
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PMID:Hormonal diagnosis of GH hypersecretory states. 1549 57

Liver transplantation is the only treatment for advanced liver cirrhosis. Therapies halting the progression of the disease are urgently needed. Administration of recombinant insulin-like growth factor-I (rIGF-I) induces hepatoprotective effects in experimental cirrhosis. Therefore, we analyzed the efficacy of a recombinant simian virus 40 vector (rSV40) encoding IGF-I (rSVIGF-I) to prevent cirrhosis progression. First, transgene expression was evaluated in mice injected with rSV40 encoding luciferase, which showed long-term hepatic expression of the transgene. Interestingly, luciferase expression increased significantly in CCl(4)-damaged livers and upon IGF-I administration, thus liver injury and IGF-I expression from rSVIGF-I should favor transgene expression. rSVIGF-I therapeutic efficacy was studied in rats where liver cirrhosis was induced by CCl(4) inhalation during 36 weeks. At the end of the study, the hepatic levels of IGF-I and IGF-binding protein 3 were higher in rSVIGF-I-treated rats than in control cirrhotic animals. Cirrhotic rats treated with rSVIGF-I had reduced serum bilirubin, transaminases and liver fibrosis scores and increased hepatic expression of hepatocyte growth factor and STAT3alpha as compared to cirrhotic animals. Furthermore, cirrhotic animals showed testis atrophy and altered spermatogenesis, whereas testicular size and histology were normal in cirrhotic rats that received rSVIGF-I. Therefore, rSV40-mediated sustained expression of IGF-I in the liver slowed cirrhosis progression.
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PMID:Liver transduction with a simian virus 40 vector encoding insulin-like growth factor I reduces hepatic damage and the development of liver cirrhosis. 1702 7


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