c-peptide and Hepatitis

Increased insulin resistance is the major pathogenic mechanism in the development of non-alcoholic steatohepatitis.. To investigate the therapeutic effect of metformin, a well-known insulin-sensitizing agent, in the treatment of non-alcoholic steatohepatitis.. Thirty-six patients with non-alcoholic steatohepatitis were randomized into two groups. The first group was given lipid and calorie-restricted dietary treatment alone, and the second group was given metformin 850 mg b.d. plus dietary treatment, for 6 months. The changes in biochemical, sonographic and histological parameters were compared.. The mean serum alanine/aspartate aminotransferase, insulin and C-peptide levels decreased and the index of insulin resistance improved significantly from baseline in the group given metformin. The mean changes in these parameters in the metformin group were significantly greater than those in the group given dietary treatment alone. Although more patients in the metformin group showed improvement in the necro-inflammatory activity, compared with the group given dietary treatment alone, no significant differences in necro-inflammatory activity or fibrosis were seen between the groups.. The data suggest that improvement of the insulin sensitivity with metformin may improve the liver disease in patients with non-alcoholic steatohepatitis.

Topics: Adult; Blood Glucose; C-Peptide; Female; Hepatitis; Humans; Hypoglycemic Agents; Insulin Resistance; Male; Metformin; Middle Aged; Steatorrhea; Treatment Outcome

Herein, we investigated the hypoglycemic effect of plant gallic acid (GA) on glucose uptake in an insulin-resistant cell culture model and on hepatic carbohydrate metabolism in rats with a high-fructose diet (HFD)-induced diabetes. Our hypothesis is that GA ameliorates hyperglycemia via alleviating hepatic insulin resistance by suppressing hepatic inflammation and improves abnormal hepatic carbohydrate metabolism by suppressing hepatic gluconeogenesis and enhancing the hepatic glycogenesis and glycolysis pathways in HFD-induced diabetic rats. Gallic acid increased glucose uptake activity by 19.2% at a concentration of 6.25 μg/mL in insulin-resistant FL83B mouse hepatocytes. In HFD-induced diabetic rats, GA significantly alleviated hyperglycemia, reduced the values of the area under the curve for glucose in an oral glucose tolerance test, and reduced the scores of the homeostasis model assessment of insulin resistance index. The levels of serum C-peptide and fructosamine and cardiovascular risk index scores were also significantly decreased in HFD rats treated with GA. Moreover, GA up-regulated the expression of hepatic insulin signal transduction-related proteins, including insulin receptor, insulin receptor substrate 1, phosphatidylinositol-3 kinase, Akt/protein kinase B, and glucose transporter 2, in HFD rats. Gallic acid also down-regulated the expression of hepatic gluconeogenesis-related proteins, such as fructose-1,6-bisphosphatase, and up-regulated expression of hepatic glycogen synthase and glycolysis-related proteins, including hexokinase, phosphofructokinase, and aldolase, in HFD rats. Our findings indicate that GA has potential as a health food ingredient to prevent diabetes mellitus.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; C-Peptide; Carbohydrate Metabolism; Cell Line; Diabetes Mellitus, Type 2; Dietary Carbohydrates; Dietary Supplements; Fructosamine; Fructose; Gallic Acid; Gene Expression Regulation; Hepatitis; Hepatocytes; Hyperglycemia; Hypoglycemic Agents; Insulin Resistance; Male; Mice; Oxidative Stress; Rats, Wistar

Nonalcoholic steatohepatitis (NASH) is a disorder characterized by hepatic steatosis, inflammation, and fibrosis. Leptin is an adipocyte-derived antiobesity hormone that in rodents prevents "lipotoxicity" by limiting triglyceride accumulation and also regulates matrix deposition (fibrosis) during wound healing. We therefore determined serum leptin levels in patients with NASH to determine whether relationships existed between leptin levels and severity of hepatic steatosis or fibrosis. We used a radioimmunoassay to determine serum [total] leptin concentrations in 27 men and 20 women with NASH and 47 controls matched for gender and body mass index (BMI; and partly for age). Serum leptin values were correlated with hepatic steatosis, fibrosis, and inflammation (each categorized semiquantitatively on liver histology), and with anthropometric indices, serum lipids, glucose, insulin, c-peptide, and alanine aminotransferase (ALT) levels. Compared with the controls, mean serum leptin levels were raised in both men and women with NASH (men 14 +/- 11 ng/mL vs. 7.2 +/- 4.1 ng/mL, P =.003; women 35 +/- 16 ng/mL vs. 15 +/- 8.2 ng/mL, P <.001). Leptin values correlated with serum c-peptide levels but not with BMI. In a multivariate analysis, serum leptin (P =.027), serum c-peptide (P =.001), and age (P =.027) were selected as independent predictors of the severity of hepatic steatosis. However, serum leptin was not an independent predictor of hepatic inflammation or fibrotic severity. In conclusion, hyperleptinemia occurs in NASH and is not explained simply by gender, obesity, or the presence of type 2 diabetes. Furthermore, leptin levels correlate directly with the severity of hepatic steatosis but not with inflammation or fibrosis. We propose that the relationship between leptin and steatosis reflects a pathogenic role of leptin in hepatic insulin resistance and/or a failure of the antisteatotic actions of leptin ("peripheral leptin resistance").

Topics: Adult; Aged; C-Peptide; Fatty Liver; Female; Hepatitis; Humans; Insulin; Insulin Resistance; Leptin; Liver Cirrhosis; Male; Middle Aged; Multivariate Analysis; Severity of Illness Index; Sex Factors; Triglycerides

Topics: Adult; C-Peptide; Fatty Liver; Female; Hepatitis; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Lipids; Liver; Male; Obesity; Reference Values

To characterize the pulsatile liberation of pancreatic hormones, blood was taken from the portal vein of four patients (three men, one woman; aged 65-71 years) with alcoholic (n = 3) or posthepatitic (n = 1) liver cirrhosis. The concentrations of glucose, insulin, C-peptide and glucagon were measured within one minute. The concentrations of insulin, C-peptide and glucagon varied considerably in intervals of 4.1-6.5 min. The swings in insulin concentration ranged between 17 and 163.5 microU/ml. Oral glucose loading with 100 g increased the insulin and C-peptide swings, but not their periodicity. This indicates that pulsatile insulin secretion is amplitude not rate driven.

Topics: Aged; Blood Glucose; C-Peptide; Catheterization, Peripheral; Female; Glucagon; Glucose; Hepatitis; Humans; Insulin; Insulin Secretion; Liver Cirrhosis; Liver Cirrhosis, Alcoholic; Male; Portal Vein; Pulsatile Flow; Radiography, Interventional; Time Factors

Topics: Acute Disease; Adult; Aged; C-Peptide; Female; Glucose Tolerance Test; Hepatitis; Humans; Insulin; Male; Middle Aged; Pancreas

Topics: Blood Glucose; C-Peptide; Chronic Disease; Glucose Tolerance Test; Hepatitis; Humans; Insulin; Insulin Secretion

In 64 patients suffering from chronic inflammatory liver disease (alcoholic hepatitis, chronic active hepatitis, chronic persistent hepatitis) significantly increased values of blood glucose and insulin, free fatty acids and C-peptide were observed during a 100 g oral glucose load. Fasting values of blood glucose, free fatty acids and C-peptide were also increased, while serum growth hormone remained unchanged. In patients with chronic active hepatitis the C-peptide/insulin-ratio, a measure for hepatic insulin degradation, was significantly lowered after glucose uptake. During oral load there were no discernible differences between the different types of chronic inflammatory liver disease concerning blood glucose, serum insulin and free fatty acids. In normal weight and in overweight patients suffering from liver disease blood glucose and serum insulin values were increased to the same extent. As it is known from the liver cirrhosis chronic inflammatory liver disease lead to an insulin resistance, to which elevated free fatty acid levels contribute. Increased body weight has no influence on the insulin resistance observed in chronic liver inflammation. From the changes of the C-peptide and the C-peptide/insulin-ratio it can be deduced, that the hyperinsulinism in patients with chronic inflammatory liver disease is due to both insulin hypersecretion and diminished hepatic insulin degradation.

Topics: Adult; Blood Glucose; Body Weight; C-Peptide; Chronic Disease; Fatty Acids, Nonesterified; Female; Glucose Tolerance Test; Hepatitis; Humans; Hyperinsulinism; Male; Middle Aged

To clarify the mechanism of hyperinsulinism of hepatic cirrhosis, plasma insulin and C-peptide levels before and after oral glucose loads were measured in 34 patients with cirrhosis, 15 patients with chronic hepatitis, and 25 normal subjects. While plasma immunoreactive insulin (IRI) levels during oral glucose tolerance testing (OGTT) were significantly increased in cirrhotics, plasma immunoreactive C-peptide (CPR) levels were elevated slightly. The C-peptide to insulin ratio throughout OGTT was significantly smaller in cirrhotics than in normal subjects (P less than 0.01). A decreased hepatic insulin degradation rate has been suggested to one of the main causes of hyperinsulinism in hepatic cirrhosis. The ratio of the difference between basal and 30-min CPR values and basal and 30-min OGTT blood glucose values [delta CPR: delta BS(30)'] as well as the delta IRI: delta BS(30') ratio was significantly decreased in cirrhotics (P less than 0.01). These results indicate that insulin secretion in response to a glycemic stimulus is reduced in cirrhotics. Both the ratios of the sums of six IRS and CPR values of OGTT (sigma CPR: sigma IRI) and delta CPR: delta BS(30') and sigma CPR: sigma BS(30') were found in inverse relationship with indocyanine green retention rate in cirrhotics.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Chronic Disease; Female; Glucose Tolerance Test; Hepatitis; Humans; Insulin; Kinetics; Liver Cirrhosis; Liver Function Tests; Male; Middle Aged

Topics: Acute Disease; C-Peptide; Hepatic Encephalopathy; Hepatitis; Hepatitis, Viral, Human; Humans; Insulin; Liver; Liver Cirrhosis; Liver Diseases; Peptides