title: Rosmarinic acid ameliorates hyperglycemia and insulin sensitivity in diabetic rats, potentially by modulating the expression of PEPCK and GLUT4.
abstract: BACKGROUND
  Rosmarinic acid (RA) is a natural substance that may be useful for treating diabetes mellitus. The present study investigated the effects of RA on glucose homeostasis and insulin regulation in rats with streptozocin (STZ)-induced type 1 diabetes or high-fat diet (HFD)-induced type 2 diabetes.
  
  
  METHODS
  Glucose homeostasis was determined using oral glucose tolerance tests and postprandial glucose tests, and insulin activity was evaluated using insulin tolerance tests and the homeostatic model assessment for insulin resistance. Additionally, the protein expression levels of PEPCK and GLUT4 were determined using Western blot analysis.
  
  
  RESULTS
  RA administration exerted a marked hypoglycemic effect on STZ-induced diabetic rats and enhanced glucose utilization and insulin sensitivity in HFD-fed diabetic rats. These effects of RA were dose-dependent. Meanwhile, RA administration reversed the STZ- and HFD-induced increase in PEPCK expression in the liver and the STZ- and HFD-induced decrease in GLUT4 expression in skeletal muscle.
  
  
  CONCLUSIONS
  RA reduces hyperglycemia and ameliorates insulin sensitivity by decreasing PEPCK expression and increasing GLUT4 expression.
authors.affiliation: Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan; Faculty of Medicine, Sam Ratulangi University, Manado, Indonesia.
authors.forename: Joshua
authors.initials: J
authors.lastname: Runtuwene
authors.affiliation: Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Kai-Chun
authors.initials: KC
authors.lastname: Cheng
authors.affiliation: Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Asakawa
authors.affiliation: Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Amitani
authors.affiliation: Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Marie
authors.initials: M
authors.lastname: Amitani
authors.affiliation: Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Morinaga
authors.affiliation: Department of Biomedical Ethics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Takimoto
authors.affiliation: Faculty of Medicine, Sam Ratulangi University, Manado, Indonesia.
authors.forename: Bernabas Harold Ralph
authors.initials: BH
authors.lastname: Kairupan
authors.affiliation: Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Inui
mesh_terms: D000818:Animals; D002934:Cinnamates / Q000378:metabolism / Q000494:pharmacology*; D053630:Depsides / Q000378:metabolism / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D059305:Diet, High-Fat; D051275:Glucose Transporter Type 4 / Q000737:chemistry / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000737:chemistry* / Q000378:metabolism*; D007333:Insulin Resistance; D018482:Muscle, Skeletal / Q000737:chemistry / Q000187:drug effects*; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000737:chemistry* / Q000378:metabolism*; D051381:Rats; D013311:Streptozocin / Q000737:chemistry / Q000494:pharmacology*; D000097123:Rosmarinic Acid
chemical_list: D002934:Cinnamates; D053630:Depsides; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D013311:Streptozocin; D000097123:Rosmarinic Acid
keywords: GLUT4; HFD; HOMA-IR; PEPCK; STZ; diabetes mellitus