Branched-chain amino acid-enriched supplementation improves insulin resistance in patients with chronic liver disease.

Increased insulin resistance is a therapeutic target in patients with chronic liver disease. Branched-chain amino acids (BCAA) have been reported to improve insulin resistance in in vivo experiments. Thus, we investigated the effects of BCAA on insulin resistance in patients with chronic liver disease. Twelve patients with chronic liver disease were enrolled. Each patient was given one sachet of a BCAA-enriched supplement after breakfast and another at bedtime. The effects of the BCAA-enriched supplementation on insulin resistance were examined 30, 60 and 90 days after administration by the homeostasis model assessment method for insulin resistance (HOMA-IR) and for beta cell function (HOMA-%B). The HOMA-IR and HOMA-%B values were elevated at baseline, however, these parameters showed no significant changes after administration of the BCAA-enriched supplement in the overall patient population. By stratification via gender, patients in the male group showed a significantly greater elevation in the HOMA-IR value compared to the female patients at baseline. After the administration, the HOMA-IR and HOMA-%B values were significantly decreased only in the male group (9.4+/-4.8 vs. 2.4+/-0.7, 657+/-345 vs. 126+/-36, respectively; P<0.05). We found that there was a gender difference in chronic viral liver disease-related insulin resistance. Moreover, a BCAA-enriched supplement improved insulin resistance and beta cell function in male patients with chronic viral liver disease. Thus, a BCAA-enriched supplement may be a useful therapeutic agent for decreasing insulin resistance in male patients with chronic viral liver disease.

[1]  T. Kawaguchi,et al.  Altered expression of glucagon‐like peptide‐1 and dipeptidyl peptidase IV in patients with HCV‐related glucose intolerance , 2008, Journal of gastroenterology and hepatology.

[2]  T. Kawaguchi,et al.  Branched‐chain amino acids improve insulin resistance in patients with hepatitis C virus‐related liver disease: report of two cases , 2007, Liver international : official journal of the International Association for the Study of the Liver.

[3]  G. Marchesini,et al.  Anticatabolic Effect of Branched‐Chain Amino Acid‐Enriched Solutions in Patients with Liver Cirrhosis , 2007, Hepatology.

[4]  T. Kawaguchi,et al.  Significance of glucose intolerance and SHIP2 expression in hepatocellular carcinoma patients with HCV infection. , 2007, Oncology reports.

[5]  P. Faure,et al.  Comparison of the effects of zinc alone and zinc associated with selenium and vitamin E on insulin sensitivity and oxidative stress in high-fructose-fed rats. , 2007, Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements.

[6]  G. Schwartz,et al.  Increasing Dietary Leucine Intake Reduces Diet-Induced Obesity and Improves Glucose and Cholesterol Metabolism in Mice via Multimechanisms , 2007, Diabetes.

[7]  T. Kawaguchi,et al.  Clearance of HCV Improves Insulin Resistance, Beta-Cell Function, and Hepatic Expression of Insulin Receptor Substrate 1 and 2 , 2007, The American Journal of Gastroenterology.

[8]  Y. Adachi,et al.  Oral administration of a zinc complex improves type 2 diabetes and metabolic syndromes. , 2006, Biochemical and biophysical research communications.

[9]  M. Plauth,et al.  ESPEN Guidelines on Enteral Nutrition: Liver disease. , 2006, Clinical nutrition.

[10]  M. Malavolti,et al.  Accuracy of eight-polar bioelectrical impedance analysis for the assessment of total and appendicular body composition in peritoneal dialysis patients , 2005, European Journal of Clinical Nutrition.

[11]  T. Kawaguchi,et al.  Causal relationship between hepatitis C virus core and the development of type 2 diabetes mellitus in a hepatitis C virus hyperendemic area: a pilot study. , 2005, International journal of molecular medicine.

[12]  Masahiko Kato,et al.  Effects of oral branched-chain amino acid granules on event-free survival in patients with liver cirrhosis. , 2005, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[13]  K. Takehana,et al.  Branched-chain amino acids improve glucose metabolism in rats with liver cirrhosis. , 2005, American journal of physiology. Gastrointestinal and liver physiology.

[14]  E. Van Obberghen,et al.  Amino acids and leucine allow insulin activation of the PKB/mTOR pathway in normal adipocytes treated with wortmannin and in adipocytes from db/db mice , 2004, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[15]  T. Kawaguchi,et al.  Hepatitis C virus down-regulates insulin receptor substrates 1 and 2 through up-regulation of suppressor of cytokine signaling 3. , 2004, The American journal of pathology.

[16]  G. Reach,et al.  Insulinotropic agent ID-1101 (4-hydroxyisoleucine) activates insulin signaling in rat. , 2004, American journal of physiology. Endocrinology and metabolism.

[17]  F. Yoshizawa,et al.  Amino Acids and Insulin Control Autophagic Proteolysis through Different Signaling Pathways in Relation to mTOR in Isolated Rat Hepatocytes* , 2004, Journal of Biological Chemistry.

[18]  M. Harada,et al.  Hydrogen peroxide overproduction in megamitochondria of troglitazone‐treated human hepatocytes , 2003, Hepatology.

[19]  I. Sonaka,et al.  Leucine promotes glucose uptake in skeletal muscles of rats. , 2002, Biochemical and biophysical research communications.

[20]  Lu-Yu Hwang,et al.  Risk factors for hepatocellular carcinoma: Synergism of alcohol with viral hepatitis and diabetes mellitus , 2002, Hepatology.

[21]  K. Uyeda,et al.  Glucose and cAMP regulate the L-type pyruvate kinase gene by phosphorylation/dephosphorylation of the carbohydrate response element binding protein , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[22]  R. Anderson,et al.  Chromium in the prevention and control of diabetes. , 2000, Diabetes & metabolism.

[23]  L. Shantz,et al.  Leucine Regulates Translation of Specific mRNAs in L6 Myoblasts through mTOR-mediated Changes in Availability of eIF4E and Phosphorylation of Ribosomal Protein S6* , 1999, The Journal of Biological Chemistry.

[24]  T. Pelikanova,et al.  [Relation between serum amino acids and insulin sensitivity (results of a clamp study in offspring of hypertensive patients]. , 1997, Vnitrni lekarstvi.

[25]  P. J. Berry.  United Kingdom prospective diabetes study (UKPDS) 13: relative efficacy of randomly allocated diet, sulphonylurea, insulin, or metformin in patients with newly diagnosed non-insulin dependent diabetes followed for three years , 1995, BMJ.

[26]  B. Ludvik,et al.  Improvement in glucose tolerance and insulin resistance in obese subjects treated with troglitazone. , 1994, The New England journal of medicine.

[27]  G. Marchesini,et al.  Prognostic significance of diabetes in patients with cirrhosis , 1994, Hepatology.

[28]  L. Moldawer,et al.  Whole-body nitrogen and tyrosine metabolism in surgical patients receiving branched-chain amino acid solutions. , 1985, Archives of surgery.

[29]  R. Turner,et al.  Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man , 1985, Diabetologia.

[30]  R. DeFronzo,et al.  Epinephrine-induced insulin resistance in man. , 1980, The Journal of clinical investigation.

[31]  G. Biserte,et al.  Developmental aspect of phenylalanine hydroxylase in the rat — hormonal influences , 1979, Mechanisms of Ageing and Development.

[32]  V. Marks,et al.  Glucose tolerance and diabetes in chronic liver disease. , 1967, Lancet.

[33]  S. Kimball,et al.  Signaling pathways and molecular mechanisms through which branched-chain amino acids mediate translational control of protein synthesis. , 2006, The Journal of nutrition.

[34]  J. Dufour,et al.  Insulin resistance is associated with liver fibrosis in non-diabetic chronic hepatitis C patients. , 2005, Journal of hepatology.

[35]  M. Heitkemper,et al.  Guidelines for the use of parenteral and enteral nutrition in adult and pediatric patients. , 2002, JPEN. Journal of parenteral and enteral nutrition.

[36]  S. Ritland,et al.  Physical activity in liver disease and liver function in sportsmen. , 1982, Scandinavian journal of social medicine. Supplementum.