title: Gallic acid ameliorates hyperglycemia and improves hepatic carbohydrate metabolism in rats fed a high-fructose diet.
abstract: 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.
authors.affiliation: Department of Food and Beverage Management, China University of Science and Technology, Taipei 11581, Taiwan.
authors.forename: Da-Wei
authors.initials: DW
authors.lastname: Huang
authors.affiliation: Graduate Institute of Food Science and Technology, National Taiwan University, Taipei 10672, Taiwan.
authors.forename: Wen-Chang
authors.initials: WC
authors.lastname: Chang
authors.affiliation: Graduate Institute of Food Science and Technology, National Taiwan University, Taipei 10672, Taiwan.
authors.forename: James Swi-Bea
authors.initials: JS
authors.lastname: Wu
authors.affiliation: Department of Human Development and Family Studies, National Taiwan Normal University, Taipei 10610, Taiwan.
authors.forename: Rui-Wen
authors.initials: RW
authors.lastname: Shih
authors.affiliation: Department of Human Development and Family Studies, National Taiwan Normal University, Taipei 10610, Taiwan. Electronic address: scs@ntnu.edu.tw.
authors.forename: Szu-Chuan
authors.initials: SC
authors.lastname: Shen
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use; D000975:Antioxidants / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D002096:C-Peptide / Q000037:antagonists & inhibitors / Q000097:blood; D050260:Carbohydrate Metabolism; D002460:Cell Line; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000178:diet therapy* / Q000276:immunology / Q000378:metabolism; D004040:Dietary Carbohydrates / Q000009:adverse effects; D019587:Dietary Supplements; D019270:Fructosamine / Q000037:antagonists & inhibitors / Q000097:blood; D005632:Fructose / Q000009:adverse effects; D005707:Gallic Acid / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D005786:Gene Expression Regulation; D006505:Hepatitis / Q000150:complications / Q000517:prevention & control; D022781:Hepatocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006943:Hyperglycemia / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D018384:Oxidative Stress; D017208:Rats, Wistar
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D002096:C-Peptide; D004040:Dietary Carbohydrates; D007004:Hypoglycemic Agents; D005632:Fructose; D019270:Fructosamine; D005707:Gallic Acid
keywords: Carbohydrate metabolism; Gallic acid; High-fructose diet; Hyperglycemia; Insulin resistance; Rat