title: Amarogentin ameliorates diabetic disorders in animal models.
abstract: Amarogentin is a bitter-tasting secoiridoid glycoside isolated from an herb. Inhibition of aldose reductase by amarogentin has been documented as an antidiabetic action. However, the mechanisms of action of amarogentin in diabetic disorders remain unknown. The present study employed streptozotocin-induced type 1 diabetic (T1DM) rats to investigate the antihyperglycemic action of amarogentin. Changes in the protein expression of glucose transporter 4 (GLUT4) and phosphoenolpyruvate carboxykinase (PEPCK) in skeletal muscle and liver, respectively, were also detected by Western blotting. Additionally, a type 2 diabetes (T2DM) animal model induced using a fructose-rich diet was also applied to assess the effect of amarogentin on insulin resistance according to the homeostasis model assessment-insulin resistance (HOMA-IR). Amarogentin dose-dependently attenuated hyperglycemia in the T1DM rats lacking insulin. The action of amarogentin was further supported in rats administered the oral glucose tolerance test. Western blotting showed that amarogentin reversed the decreased GLUT4 level in skeletal muscle and reduced the elevated PEPCK expression in livers isolated from the T1DM rats. Moreover, amarogentin decreased the HOMA-IR and increased insulin sensitivity in the T2DM rats. These data show that amarogentin may ameliorate glucose homeostasis in diabetic rats, indicating its potential for future development as an antidiabetic drug.
authors.affiliation: Department of Nursing, Tzu Chi University of Science and Technology, Hualien City, 97005, Taiwan.
authors.forename: Ho-Shan
authors.initials: HS
authors.lastname: Niu
authors.affiliation: Bachelor Program of Senior Services, College of Humanities and Social Sciences, Southern Taiwan University of Science and Technology, Yong Kang, Tainan City, 71005, Taiwan.
authors.forename: Pin-Chun
authors.initials: PC
authors.lastname: Chao
authors.affiliation: Department of Cardiology, Chi-Mei Medical Center, Yong Kang, Tainan City, 71003, Taiwan.|Department of Medical Research, Chi-Mei Medical Center, Yong Kang, Tainan City, 71003, Taiwan.
authors.forename: Po-Ming
authors.initials: PM
authors.lastname: Ku
authors.affiliation: Department of Nursing, Tzu Chi University of Science and Technology, Hualien City, 97005, Taiwan.
authors.forename: Chiang-Shan
authors.initials: CS
authors.lastname: Niu
authors.affiliation: Department of Surgery, Pingtung Hospital, Division of Neurosurgery, Kaohsiung Medical University Chung-Ho Memorial Hospital, School of Medicine, Kaohsiung Medical University, Kaohsiung City, 81201, Taiwan.
authors.forename: Kung-Shing
authors.initials: KS
authors.lastname: Lee
authors.affiliation: Department of Medical Research, Chi-Mei Medical Center, Yong Kang, Tainan City, 71003, Taiwan. jtcheng@mail.cjcu.edu.tw.|Institute of Medical Sciences, Chang Jung Christian University, Gueiren, Tainan City, 71101, Taiwan. jtcheng@mail.cjcu.edu.tw.
authors.forename: Juei-Tang
authors.initials: JT
authors.lastname: Cheng
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology; D004040:Dietary Carbohydrates; D004305:Dose-Response Relationship, Drug; D005632:Fructose; D005951:Glucose Tolerance Test; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D039823:Iridoids / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000378:metabolism; D017208:Rats, Wistar; D013311:Streptozocin
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D004040:Dietary Carbohydrates; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; D039823:Iridoids; C495694:Slc2a4 protein, rat; D005632:Fructose; C102609:amarogentin; D013311:Streptozocin; C582554:Pck1 protein, rat; D010729:Phosphoenolpyruvate Carboxykinase (GTP)
keywords: Amarogentin; Fructose-rich chow; Insulin resistance; Insulin-independent action; Rats; Streptozotocin