Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

High-calorie total parenteral nutrition (TPN) is associated with hepatic dysfunction and steatosis. Because TPN-induced steatosis might compromise hepatic expression of insulin-like growth factor-I (IGF-I) and thereby limit its potential nutritional benefit, we examined hormonal and IGF-I responses in male Sprague-Dawley rats (270 to 300 g) fed by continuous intravenous infusion with high-calorie, high-dextrose (350 kcal/kg) TPN solutions for O (control), 2, 4, and 8 days. Since IGF-binding proteins (IGFBPs) are thought to modulate the biological effects of IGFs in target tissues, we also determined serum levels of IGFBPs. Animals developed hepatic steatosis after 2 to 8 days of TPN, as reflected by a sevenfold to 15-fold increase in hepatic triacylglycerol content (P < .001 v control on each day). Serum corticosterone and insulin levels were significantly higher after 2 and 4 days of TPN, whereas serum growth hormone levels were reduced after 4 and 8 days. Serum IGF-I levels were not significantly different during TPN. However, there was a coordinate reduction in the three major hepatic IGF-I transcripts (7.0, 1.9, and 1.0 kb) after 2, 4, or 8 days of TPN, and IGF-I transcripts corresponding to multiple initiation sites within exons 1 and 2 were coordinately downregulated with TPN. Western ligand blotting indicated that serum levels of 38K to 43K, 30K to 34K, and 24K IGFBPs were increased approximately twofold after 4 and 8 days of TPN as compared with control values.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:High-calorie total parenteral nutrition reduces hepatic insulin-like growth factor-I mRNA and alters serum levels of insulin-like growth factor-binding protein-1, -3, -5, and -6 in the rat. 753 78

Empirical evidence suggests that prolonged underfeeding of protein to late-pregnant dry cows can have modest negative carry-over effects on milk volume and/or protein yield during early lactation, and may also cause increased incidence of metabolic diseases associated with fatty liver. However, assessment of requirements is hampered by lack of information on relationships between dietary intake of crude protein (N x 6.25) and metabolizable protein supply during late pregnancy, and by incomplete understanding of the quantitative metabolism of amino acids in maternal and conceptus tissues. Inability of the postparturient cow to consume sufficient protein to meet mammary and extra-mammary amino acid requirements, including a significant demand for hepatic gluconeogenesis, necessitates a substantial, albeit transient, mobilization of tissue protein during the first 2 weeks of lactation. Ultimately, much of this mobilized protein appears to be derived from peripheral tissues, especially skeletal muscle and, to a lesser extent, skin, through suppression of tissue protein synthesis, and possibly increased proteolysis. In the shorter term, soon after calving, it is likely that amino acids required for hepatic glucose synthesis are diverted from high rates of synthesis of splanchnic tissue and export proteins, including serum albumin. The prevailing endocrine milieu of the periparturient cow, including major reductions in plasma levels of insulin and insulin-like growth factor-I, together with insulin resistance in peripheral tissues, must permissively facilitate, if not actively promote, net mobilization of amino acids from these tissues.
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PMID:Protein nutrition in late pregnancy, maternal protein reserves and lactation performance in dairy cows. 1082 81

Growth hormone (GH) and insulin-like growth factor-I (IGF-I) play essential roles in growth in childhood, and continue to have important metabolic actions in adults. Adult growth hormone deficiency (AGHD) is characterized by increased visceral adiposity, abnormal lipid profiles, premature atherosclerosis, decreased quality of life, and increased mortality. Recently, case reports and several clinical studies suggest that GHD state in adults is associated with an increased prevalence of nonalcoholic fatty liver disease (NAFLD) and progression to nonalcoholic steatohepatitis (NASH) or liver cirrhosis. As a mechanistic insight, growing evidence has revealed that GH as well as IGF-I play essential roles in the liver. Further investigation is necessary to clarify the precise mechanisms by which GH and IGF-I exert their effects in the liver; however, it should be noted that NAFLD/NASH has emerged as an important comorbidity in AGHD.
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PMID:Essential roles of growth hormone (GH) and insulin-like growth factor-I (IGF-I) in the liver. 2298 86

Recent studies have elucidated a lower level of serum insulin-like growth factor-I (IGF-I) or a decrease in the IGF-I/IGF-binding protein-3 (IGFBP-3) ratio in patients with type 2 diabetes mellitus or hepatic steatosis. Persistent hepatitis C virus (HCV) infection often evokes metabolic abnormalities including hepatic steatosis and insulin resistance. We hypothesized that the relationship between the ratio of IGF-I/IGFBP-3 and the severity of hepatic steatosis or insulin resistance would be observed in patients with HCV-related chronic liver disease (CLD). On the basis of the classifications proposed by Brunt and colleagues (Am J Gastroenterol 1999; 94: 2467-2474), among the 42 enrolled patients with HCV-related CLD, 23 of them had no hepatic steatosis (grade 0), 14 had grade 1 steatosis, and 5 had grade 2 steatosis. The levels of serum IGF-I in the enrolled patients declined in proportion to the severity of hepatic steatosis, whereas serum IGFBP-3 levels did not affect its severity. Therefore, the ratio of IGF-I/IGFBP-3, which corresponds to the circulating free IGF-I status, was significantly lower in those patients with hepatic steatosis (grades 1 and 2) than in those without hepatic steatosis. Serum IGF-I levels significantly correlated with serum zinc levels (r = 0.370, P = .0266), but IGFBP-3 levels did not. However, the linear regression analysis revealed an inverse correlation between the IGF/IGFBP-3 ratio and the value of homeostasis model for assessment of insulin resistance (r =-0.411, P = .0094). These findings suggest that the decline of the circulating free IGF-I level, which derives from zinc deficiency, may contribute to hepatic steatosis and insulin resistance in patients with HCV-related CLD.
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PMID:The ratio of insulin-like growth factor-I/insulin-like growth factor-binding protein-3 in sera of patients with hepatitis C virus-related chronic liver disease as a predictive marker of insulin resistance. 2335 7

Evidence of an emerging etiologic link between diabetes mellitus and several gastrointestinal malignancies is presented. Although a correlation between pancreatic cancer and diabetes mellitus has long been suspected, the potential role diabetes mellitus plays in the pathogenicity of both hepatocellular carcinoma and colon cancer is becoming increasingly well defined. Further supporting the prospect of etiologic linkage, the association of diabetes mellitus with colon cancer is consistently demonstrated to be independent of obesity. An increasing incidence of diabetes and obesity in the United States has led to a recent surge in incidence of hepatocellular cancer on the background of nonalcoholic fatty liver disease, and this disease is expected to commensurately grow in incidence. Widespread recognition of this emerging risk factor may lead to a change in screening practices. Although the mechanisms underlying the correlation are still under investigation, the role of insulin, the insulin-like growth factor-I, and related binding and signaling pathways as regulators of cell growth and cell proliferation are implicated in carcinogenesis and tumor growth. The potential role of metformin and other medications for diabetes mellitus in the chemoprevention, carcinogenesis, and treatment of gastrointestinal malignancies is also presented.
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PMID:Diabetes mellitus as a novel risk factor for gastrointestinal malignancies. 2541 39

Chronic liver diseases (CLDs) encompass a wide range of illnesses, including nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, and viral hepatitis. Deterioration of liver capacity, with subsequent progression into cirrhosis and hepatocellular carcinoma (HCC), ultimately leads to a further decrease in the hepatic reserve. The Child-Turcotte-Pugh scoring system is the standard tool for assessing underlying liver reserve capacity in routine practice and in clinical trials of CLD and HCC. In this review, we highlight the clinical significance of insulin-like growth factor-I (IGF-I) and the growth hormone (GH) signaling pathway in HCC. IGF-I could be a marker for liver reserve capacity in CLDs and HCC in clinical practice. This approach could improve the risk assessment and stratifications of patients on the basis of their underlying liver reserve, either before active treatment in routine practice or before they are enrolled in clinical trials.
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PMID:Type I insulin-like growth factor as a liver reserve assessment tool in hepatocellular carcinoma. 2750 2