PubTransformer

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PMID- 28403934
OWN - NLM
STAT- MEDLINE
DA  - 20170413
DCOM- 20170419
LR  - 20170419
IS  - 1532-8600 (Electronic)
IS  - 0026-0495 (Linking)
VI  - 70
DP  - 2017 May
TI  - A synthetic Nitraria alkaloid, isonitramine protects pancreatic beta-cell and
      attenuates postprandial hyperglycemia.
PG  - 107-115
LID - S0026-0495(17)30049-5 [pii]
LID - 10.1016/j.metabol.2017.02.002 [doi]
AB  - OBJECTIVE: 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. METHODS:
      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. RESULTS: Isonitramine exerted
      significant inhibitory effect on alpha-glucosidases but not alpha-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. CONCLUSION:
      Taken together, isonitramine inhibited alpha-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.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Kwon, So Jung
AU  - Kwon SJ
AD  - College of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research,
      Inje University, 607 Obang-dong, Gimhae, Gyungnam, 621-749, South Korea.
FAU - Hwang, Su Jung
AU  - Hwang SJ
AD  - 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.
FAU - Jung, Yeonghun
AU  - Jung Y
AD  - 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.
FAU - Park, Hyeung-Geun
AU  - Park HG
AD  - Research Institute of Pharmaceutical Science and College of Pharmacy, Seoul
      National University, Seoul, 151-742, South Korea.
FAU - Kim, Mi-Hyun
AU  - Kim MH
AD  - College of Pharmacy, Gachon University, Hambakmoeiro 191, Yeonsu-gu, Incheon,
      406-799, South Korea.
FAU - Park, Yohan
AU  - Park Y
AD  - 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: [email protected]
FAU - Lee, Hyo-Jong
AU  - Lee HJ
AD  - 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: [email protected]
LA  - eng
PT  - Journal Article
DEP - 20170210
PL  - United States
TA  - Metabolism
JT  - Metabolism: clinical and experimental
JID - 0375267
RN  - 0 (Alkaloids)
RN  - 0 (Aniline Compounds)
RN  - 0 (Glycoside Hydrolase Inhibitors)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Nitrobenzenes)
RN  - 0 (Plant Extracts)
RN  - 0 (Protective Agents)
RN  - EC 4.1.1.49 (Phosphoenolpyruvate Carboxykinase (ATP))
RN  - GJ18911991 (nitramine)
SB  - IM
MH  - Alkaloids/isolation & purification/*pharmacology
MH  - Aniline Compounds/isolation & purification/*pharmacology
MH  - Animals
MH  - Carbohydrate Metabolism/drug effects
MH  - Cell Line
MH  - Cricetinae
MH  - Glycoside Hydrolase Inhibitors
MH  - Humans
MH  - Hyperglycemia/*drug therapy
MH  - Hypoglycemic Agents/isolation & purification/pharmacology
MH  - Insulin-Secreting Cells/*drug effects
MH  - Nitrobenzenes/isolation & purification/*pharmacology
MH  - Phosphoenolpyruvate Carboxykinase (ATP)/drug effects
MH  - Plant Extracts/chemistry
MH  - Protective Agents/isolation & purification/pharmacology
MH  - Rats
MH  - Swine
MH  - Zebrafish
OTO - NOTNLM
OT  - Diabetes mellitus
OT  - Insulin
OT  - Isonitramine
OT  - PEPCK
OT  - alpha-amylase
OT  - alpha-glucosidase
EDAT- 2017/04/14 06:00
MHDA- 2017/04/20 06:00
CRDT- 2017/04/14 06:00
PHST- 2016/08/29 [received]
PHST- 2017/01/07 [revised]
PHST- 2017/02/02 [accepted]
AID - S0026-0495(17)30049-5 [pii]
AID - 10.1016/j.metabol.2017.02.002 [doi]
PST - ppublish
SO  - Metabolism. 2017 May;70:107-115. doi: 10.1016/j.metabol.2017.02.002. Epub 2017
      Feb 10.

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