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Metabolism. 2017 May;70:107-115. doi: 10.1016/j.metabol.2017.02.002. Epub 2017 Feb 10.

A synthetic Nitraria alkaloid, isonitramine protects pancreatic β-cell and attenuates postprandial hyperglycemia.

Author information

1
College of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research, Inje University, 607 Obang-dong, Gimhae, Gyungnam, 621-749, South Korea.
2
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.
3
Research Institute of Pharmaceutical Science and College of Pharmacy, Seoul National University, Seoul, 151-742, South Korea.
4
College of Pharmacy, Gachon University, Hambakmoeiro 191, Yeonsu-gu, Incheon, 406-799, South Korea.
5
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.
6
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.

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.

KEYWORDS:

Diabetes mellitus; Insulin; Isonitramine; PEPCK; α-amylase; α-glucosidase

PMID:
28403934
DOI:
10.1016/j.metabol.2017.02.002
[Indexed for MEDLINE]

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