Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetes mellitus is a independent risk factor for the hepatitis C and for the hepatocellular carcinoma. Fatty liver is a obviously finding in patients with type 2 diabetes. It can develop steatofibrosis, steatohepatitis or liver cirrhosis. Steatohepatitis may be affected with weight reduction, metformin, rosiglitazon, or orlistat.
 ...
PMID:[Diabetes mellitus and liver diseases]. 1530 36

Epidemiological studies have shown that obesity is a risk factor for hepatocellular carcinoma. Similar studies further indicate that diabetes is also a major risk factor. Both obesity and diabetes are frequently associated with nonalcoholic fatty liver disease, and case reports have shown progression of nonalcoholic fatty liver disease to cirrhosis and hepatocellular carcinoma. Although no study has clearly tied all of these variables together, it is likely that the association of hepatocellular carcinoma with obesity represents the progression of underlying nonalcoholic fatty liver disease to cirrhosis. The mechanism most likely involves replicative senescence of steatotic mature hepatocytes and compensatory hyperplasia of progenitor (oval) cells as a reaction to chronic injury due to ongoing nonalcoholic steatohepatitis and resultant hepatic fibrosis. Growth factors associated with chronic inflammation, type 2 diabetes, and DNA mutations as a result of lipid peroxidation probably play significant roles in clonal expansion and hepatocellular carcinoma progression. It remains unclear whether cirrhosis is a prerequisite for the development of hepatocellular carcinoma or whether hepatocellular carcinoma can develop in fatty liver in the absence of cirrhosis. However, well-documented case reports suggest that most cases of hepatocellular carcinoma arise in the setting of nonalcoholic steatohepatitis with cirrhosis. Whether therapy aimed at nonalcoholic fatty liver disease reduces the risk of hepatocellular carcinoma remains to be shown. Prophylactic measures and the role of cancer surveillance have not been adequately investigated, but current evidence suggests a risk for hepatocellular carcinoma in nonalcoholic steatohepatitis-related cirrhosis that rivals that of hepatocellular carcinoma in hepatitis C virus-related cirrhosis, particularly in older male patients.
 ...
PMID:Obesity and hepatocellular carcinoma. 1550 9

The hepatitis C virus (HCV) infection is a worldwide disease that is characterized by a preferential chronic evolution with mild to severe liver disease, including cirrhosis and, in lesser proportion, hepatocarcinoma. Out of these complications, HCV is frequently reported to complicate extrahepatic manifestations. Among those associated to HCV infection with a high degree of certainty, mixed cryoglobulinemia and its complications (skin, neurological, renal, rheumatological involvement) are the most prevalent (50%) in HCV-infected patients. The other diseases include noncryoglobulinemic systemic vasculitis, splenic lymphoma with villous lymphocytes, fatigue, porphyria cutanea tarda, sicca syndrome, and autoantibodies production. The extrahepatic manifestations that share mild-degree certainty of association with HCV infection include B-cell non-Hodgkin lymphoma, autoimmune thrombocytopenia, pruritus, and type II diabetes mellitus. The other diseases such as autoimmune thyroiditis, lichen planus are more questionable for their eventual association with HCV and others (pulmonary fibrosis with or without polymyositis, progressive encephalomyelitis, Mooren's corneal ulcers, erythema nodosum, chronic polyradiculonevritis) are mostly case reports. Howerver, even in cases of tight association, the mechanisms through which HCV may promote or induce extrahepatic manifestations remain unclear and merit further investigations.
 ...
PMID:Hepatitis C virus-associated extrahepatic manifestations: a review. 1555 28

There is good evidence from in vitro studies that green tea catechins have a role in protection against degenerative diseases. However, the concentrations used in vitro are often higher than those found in animal or human plasma, and so in vivo evidence is required to demonstrate any protective effect of catechins. This article summarizes the most interesting in vivo animal studies on the protective effects of green tea catechins against biomarkers for cancer, cardiovascular disease, and other degenerative diseases. Generally, most studies using animal models show that consumption of green tea (catechins) provides some protection, although most studies have not examined dose response. Tea catechins could act as antitumorigenic agents and as immune modulators in immunodysfunction caused by transplanted tumors or by carcinogen treatment. Green tea has antiproliferative activity in hepatoma cells and hypolipidemic activity in hepatoma-treated rats, and some studies report that it prevents hepatoxicity. It could act as a preventive agent against mammary cancer postinitiation. Nevertheless, the implications of green tea catechins in preventing metastasis have not been clearly established. Long-term feeding of tea catechins could be beneficial for the suppression of high-fat diet-induced obesity by modulating lipid metabolism, could have a beneficial effect against lipid and glucose metabolism disorders implicated in type 2 diabetes, and could also reduce the risk of coronary disease. Further investigations on mechanisms, the nature of the active compounds, and appropriate dose levels are needed.
 ...
PMID:A review of the health effects of green tea catechins in in vivo animal models. 1557 50

Diabetes mellitus is the fifth leading cause of death in the United States; 17 million people are affected. Liver disease is one of the leading causes of death in persons with type 2 diabetes. The standardized mortality rate for death from liver disease is greater than that for cardiovascular disease. The spectrum of liver disease in type 2 diabetes ranges from nonalcoholic fatty liver disease to cirrhosis and hepatocellular carcinoma. The incidence of hepatitis C and acute liver failure is also increased. Nonalcoholic fatty liver disease is now considered part of the metabolic syndrome, and, with alcohol and hepatitis C, is the most common cause of chronic liver disease in the United States. Weight reduction and exercise are the mainstays of treatment for nonalcoholic fatty liver disease, but there are promising results with the new thiazolidinediones (pioglitazone and rosiglitazone) as well as metformin and 3-hydroxy-3-methylglutaryl coenzyme A inhibitors.
 ...
PMID:Narrative review: hepatobiliary disease in type 2 diabetes mellitus. 1561 92

Nonalcoholic steatohepatitis and chronic viral hepatitis C are the two dominant liver diseases in the Netherlands. Hepatic steatosis is usually innocuous but in twenty percent of patients it develops into steatohepatitis. One-fifth of these patients develop liver cirrhosis and hepatocellular carcinoma can also be a consequence of the disease. Nonalcoholic steatohepatitis is characterized by macrovesicular steatosis, necroinflammation, loss ofhepatocytes and fibrosis. Nonalcoholic steatohepatitis often is associated with type 2 diabetes mellitus, hypertension, dyslipoproteinemia and obesity. Insulin resistance plays a major role in the pathogenesis of this disease. Drugs against insulin resistance can ameliorate nonalcoholic steatohepatitis. Gradual weight loss, a diet including polyunsaturated fatty acids and exercise are other important treatment components of this condition.
 ...
PMID:[Nonalcoholic steatohepatitis: diagnosis, pathogenesis, treatment and prognosis]. 1583 33

Growth hormone (GH) and insulin are important regulators of cellular and whole body metabolism as well as somatic growth and body composition. Studies have indicated complex feedback effects of GH on insulin action and of insulin on GH signaling pathways. Previous studies in our laboratory have shown that GH induction of signal transducers and activators of transcription (STAT)5B tyrosine phosphorylation is inhibited by prolonged insulin treatment, probably via downregulation of GHR. Here, we find that in rat H4IIE hepatoma cells GH-induced tyrosine phosphorylation of two other STATs (STAT3 and STAT1) was also greatly reduced following prolonged insulin pretreatment compared with that induced by GH alone. In the present work, total STAT5B and STAT1 protein levels were not altered by prolonged insulin treatment. However, prolonged insulin treatment (16 h; 10 or 100 nM) resulted in a 30-40% reduction of total STAT3 protein, with little change at 0.1 and 1.0 nM insulin. Thus, there is a selective reduction of total STAT3 protein levels by insulin, but only at high concentration of insulin. Basal tyrosine phosphorylated (PY)-STAT3 was also significantly reduced by prolonged insulin treatment, and to a greater extent than total STAT3 protein levels. The inhibitory effect of insulin on total STAT3 protein and basal PY-STAT3 levels was dependent on activation of the MEK-ERK pathway, rather than the PI3K pathway. In contrast, the MEK-ERK pathway did not play a major role in insulin's inhibition of GH-induced PY-STAT3 and PY-STAT1. The present studies indicate that prolonged hyperinsulinemia, such as that found in some obese patients or patients with Type 2 diabetes mellitus, may have profound effects on GH signaling via STAT3 and STAT1.
 ...
PMID:Prolonged insulin treatment inhibits GH signaling via STAT3 and STAT1. 1574 7

Acute hyperglycemia normally suppresses hepatic glucose production (HGP) and gluconeogenic gene expression. Conversely, chronic hyperglycemia is accompanied by progressive increases in basal HGP and is a major contributor to hyperglycemia in both type 1 and type 2 diabetes by mechanisms that are poorly understood. The aim of this study was to investigate the molecular mechanisms whereby hyperglycemia contributes to excessive gluconeogenesis in Fao hepatoma cells. Increasing glucose from 5 to 20 mmol/l resulted in loss of glucose inhibition of PEPCK gene expression after 12 h. Furthermore, 24 h of incubation with 20 mmol/l glucose increased cAMP-stimulated PEPCK mRNA by approximately 40% (P < 0.05) and similarly increased glucose production. Although total CCAAT/enhancer-binding protein beta (C/EBPbeta) protein levels were suppressed, 20 mmol/l glucose increased the liver activating protein (LAP; an active isoform of C/EBPbeta)/liver inhibitory protein (LIP; an inhibitory isoform of C/EBPbeta) ratio significantly. Chromatin immunoprecipitation studies of the endogenous PEPCK gene demonstrated an increased association of LAP with the cAMP response element of the promoter. Using transient transfection to manipulate the LAP/LIP ratio, we also demonstrate a direct relationship between this ratio and PEPCK promoter activity. An increased LAP/LIP ratio not only enhanced cAMP- and dexamethasone-induced PEPCK gene expression but also impaired the repressive effect of insulin. These results demonstrate that sustained hyperglycemia diminishes the inhibitory effect of glucose and insulin on PEPCK expression and enhances hormone-stimulated PEPCK gene expression and hepatocellular glucose production. Because prolonged hyperglycemia increases the LAP/LIP ratio and can potentiate hormone induction of PEPCK transcription, our results suggest that a hyperglycemia-driven increased LAP/LIP ratio may be a critical molecular event in the pathogenesis of increased HGP in diabetes.
 ...
PMID:Chronic hyperglycemia enhances PEPCK gene expression and hepatocellular glucose production via elevated liver activating protein/liver inhibitory protein ratio. 1579 35

Hepatic steatosis is the hallmark of nonalcoholic fatty liver disease (NAFLD), which is the consequence of multiple metabolic derangements among which insulin resistance plays a pivotal role. Steatosis is, also, a feature of hepatitis C virus (HCV) infection. However, in chronic hepatitis C, the prevalence of steatosis is 2.5-fold more elevated than that expected by a chance concurrence with NAFLD, suggesting that HCV may be implied in the development of steatosis. As observed in NAFLD, in patients infected with HCV genotype 1 steatosis is associated with an increased body mass index. On the other hand, in patients infected with genotype 3 the extent of steatosis strictly correlates with the viral load indicating that steatosis is mainly "virus-related". Regardless of the "metabolic" or "viral" etiology, hepatic steatosis in HCV contributes to the progression of liver fibrosis, to the development of hepatocellular carcinoma and to an impaired response to interferon treatment. Features such as obesity, insulin resistance and type 2 diabetes mellitus are shared by NAFLD and HCV-associated steatosis. In addition, HCV infection, directly or through steatosis, favors the development of type 2 diabetes mellitus. Hyperlipidemia is an independent predictor of the development of NAFLD, but not of HCV-associated steatosis. Arterial hypertension is common in nonalcoholic steatohepatitis patients, and HCV infection has recently been acknowledged as an independent risk factor for atherosclerosis. The role of iron in the progression of both NAFLD and HCV-associated steatosis remains controversial while lipoperoxidation and oxidative stress are pathogenic mechanisms shared by both. Some metabolic risk factors may be shared by both HCV-associated steatosis and NAFLD although the disease progression and pathophysiological background may be different. Preliminary data suggest that the therapeutic options for NAFLD may also be useful to improve HCV-associated steatosis.
 ...
PMID:[Hepatitis C virus-associated and metabolic steatosis. Different or overlapping diseases?]. 1585 90

Although the target of hepatitis C virus (HCV) infection is the liver, it has become progressively more evident that HCV can induce diseases in numerous organs. Recently, much attention has been drawn to metabolic disorders in HCV infection. Initially, hepatic steatosis and disturbances in lipid metabolism were found to be characteristic of HCV infection, and, subsequently, a correlation was noted between HCV infection and diabetes. It is now evident that HCV, by itself, can induce insulin resistance by way of disturbing the intracellular signaling pathway of insulin by the function of HCV core protein. Insulin resistance, caused by HCV infection, evolves to type 2 diabetes when superimposed on a high-fat diet and obesity. The fact that HCV infection induces insulin resistance by the virus itself may influence the progression of chronic hepatitis and open up novel therapeutic approaches. When hepatitis C is compared with nonalcoholic steatohepatitis (NASH), there are a number of similarities and several differences. From the metabolic aspect, hepatitis C resembles NASH in numerous features, such as the presence of steatosis, serum dyslipidemia, and oxidative stress in the liver, suggesting that hepatitis C is a steatohepatitis. In contrast, there are noticeable differences between hepatitis C and NASH, in that HCV modulates cellular gene expression and intracellular signal transduction, including the activation of mitogen-activated protein (MAP) kinase and transcription factor activator protein (AP)-1, while such details have not been noted for NASH. This difference may explain the markedly higher incidence of HCC development in chronic hepatitis C compared with that in NASH. HCV infection needs to be viewed not only as a liver disease but also as a metabolic disease, and this viewpoint could open up a novel way to the molecular understanding of the pathogenesis of hepatitis C, as a virus-associated steatohepatitis (VASH).
 ...
PMID:Metabolic aspects of hepatitis C viral infection: steatohepatitis resembling but distinct from NASH. 1586 69


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>