title: A synthetic Nitraria alkaloid, isonitramine protects pancreatic β-cell and attenuates postprandial hyperglycemia.
abstract: The extracts of Nitraria genus are composed of Nitraria alkaloids and have been used traditionally as a hypoglycemic medicine. However, the efficacy and precise mechanism of Nitraria alkaloids remain largely unknown.
  
  
  
  Previously, we reported the total synthesis of (+)-isonitramine, one of Nitraria alkaloids. In this study, we investigated the anti-diabetic potential of isonitramine in diabetes mellitus and its underlying molecular mechanism in carbohydrate catabolism in vitro and in vivo.
  
  
  
  Isonitramine exerted significant inhibitory effect on α-glucosidases but not α-amylase in vitro. In zebrafish, isonitramine alleviated the streptozotocin (STZ)-induced postprandial hyperglycemia and protected the pancreatic damages against alloxan-induced oxidative stress in vivo. Also, isonitramine induced insulin without any toxicities and downregulated phosphoenolpyruvate carboxykinase (PEPCK), which catalyzes the first committed step in gluconeogenesis.
  
  
  
  Taken together, isonitramine inhibited α-glucosidase activity and PEPCK expression, while increased insulin expression, resulting in attenuating the postprandial hyperglycemia. Also, isonitramine protected the pancreas from ROS-mediated toxicities. Therefore, isonitramine may be a new drug candidate for the treatment of diabetes mellitus.
authors.affiliation: College of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research, Inje University, 607 Obang-dong, Gimhae, Gyungnam, 621-749, South Korea.
authors.forename: So Jung
authors.initials: SJ
authors.lastname: Kwon
authors.affiliation: College of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research, Inje University, 607 Obang-dong, Gimhae, Gyungnam, 621-749, South Korea; u-Healthcare & Anti-aging Research Center (u-HARC), Inje University, Gyeongnam, South Korea.
authors.forename: Su Jung
authors.initials: SJ
authors.lastname: Hwang
authors.affiliation: College of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research, Inje University, 607 Obang-dong, Gimhae, Gyungnam, 621-749, South Korea; u-Healthcare & Anti-aging Research Center (u-HARC), Inje University, Gyeongnam, South Korea.
authors.forename: Yeonghun
authors.initials: Y
authors.lastname: Jung
authors.affiliation: Research Institute of Pharmaceutical Science and College of Pharmacy, Seoul National University, Seoul, 151-742, South Korea.
authors.forename: Hyeung-Geun
authors.initials: HG
authors.lastname: Park
authors.affiliation: College of Pharmacy, Gachon University, Hambakmoeiro 191, Yeonsu-gu, Incheon, 406-799, South Korea.
authors.forename: Mi-Hyun
authors.initials: MH
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research, Inje University, 607 Obang-dong, Gimhae, Gyungnam, 621-749, South Korea; u-Healthcare & Anti-aging Research Center (u-HARC), Inje University, Gyeongnam, South Korea. Electronic address: yohanpark@inje.ac.kr.
authors.forename: Yohan
authors.initials: Y
authors.lastname: Park
authors.affiliation: College of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research, Inje University, 607 Obang-dong, Gimhae, Gyungnam, 621-749, South Korea; u-Healthcare & Anti-aging Research Center (u-HARC), Inje University, Gyeongnam, South Korea. Electronic address: hjlee@inje.ac.kr.
authors.forename: Hyo-Jong
authors.initials: HJ
authors.lastname: Lee
mesh_terms: D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology*; D000814:Aniline Compounds / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D050260:Carbohydrate Metabolism / Q000187:drug effects; D002460:Cell Line; D006224:Cricetinae; D065089:Glycoside Hydrolase Inhibitors; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000302:isolation & purification / Q000494:pharmacology; D050417:Insulin-Secreting Cells / Q000187:drug effects*; D009578:Nitrobenzenes / Q000302:isolation & purification / Q000494:pharmacology*; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry; D020011:Protective Agents / Q000302:isolation & purification / Q000494:pharmacology; D051381:Rats; D013552:Swine; D015027:Zebrafish
chemical_list: D000470:Alkaloids; D000814:Aniline Compounds; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D009578:Nitrobenzenes; D010936:Plant Extracts; D020011:Protective Agents; D019764:Phosphoenolpyruvate Carboxykinase (ATP); C015384:nitramine
keywords: Diabetes mellitus; Insulin; Isonitramine; PEPCK; α-amylase; α-glucosidase