PUBLICATION
A synthetic Nitraria alkaloid, isonitramine protects pancreatic β-cell and attenuates postprandial hyperglycemia
- Authors
- Kwon, S.J., Hwang, S.J., Jung, Y., Park, H.G., Kim, M.H., Park, Y., Lee, H.J.
- ID
- ZDB-PUB-170414-9
- Date
- 2017
- Source
- Metabolism: clinical and experimental 70: 107-115 (Journal)
- Registered Authors
- Keywords
- Diabetes mellitus, Insulin, Isonitramine, PEPCK, α-amylase, α-glucosidase
- MeSH Terms
-
- Alkaloids/isolation & purification
- Alkaloids/pharmacology*
- Aniline Compounds/isolation & purification
- Aniline Compounds/pharmacology*
- Animals
- Carbohydrate Metabolism/drug effects
- Cell Line
- Cricetinae
- Glycoside Hydrolase Inhibitors
- Humans
- Hyperglycemia/drug therapy*
- Hypoglycemic Agents/isolation & purification
- Hypoglycemic Agents/pharmacology
- Insulin-Secreting Cells/drug effects*
- Nitrobenzenes/isolation & purification
- Nitrobenzenes/pharmacology*
- Phosphoenolpyruvate Carboxykinase (ATP)/drug effects
- Plant Extracts/chemistry
- Protective Agents/isolation & purification
- Protective Agents/pharmacology
- Rats
- Swine
- Zebrafish
- PubMed
- 28403934 Full text @ Metab. Clin. Exp.
Citation
Kwon, S.J., Hwang, S.J., Jung, Y., Park, H.G., Kim, M.H., Park, Y., Lee, H.J. (2017) A synthetic Nitraria alkaloid, isonitramine protects pancreatic β-cell and attenuates postprandial hyperglycemia. Metabolism: clinical and experimental. 70:107-115.
Abstract
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 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.
Conclusion 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping