日本薬理学会年会要旨集
Online ISSN : 2435-4953
WCP2018 (The 18th World Congress of Basic and Clinical Pharmacology)
セッションID: WCP2018_PO4-9-11
会議情報

Poster session
Increased Hepatic Triglyceride Level Induced by a Glucokinase Activator in Mice
Junichi NamekawaMari YasuiAtsuko KatayanagiMitsuyuki ShiraiFumitoshi Asai
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会議録・要旨集 オープンアクセス

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Glucokinase (GK) is an enzyme that catalyzes the phosphorylation of glucose to glucose-6-phosphate, and plays an important role in maintaining glucose homeostasis by regulating secretion of insulin from pancreatic beta-cells and glucose metabolism in the liver. Recently, GK activators are expected as a novel therapeutic agent for T2DM. However, the increase in plasma TG levels is one of the major issues for the development of GK activators. In this study, we evaluated the effects of the GK activator GKA50 on the plasma and hepatic TG in mice. Male CD-1 mice received a single oral dose of vehicle or GKA50 at 15, 30, or 60 mg/kg, and plasma glucose and insulin levels were measured. Next, CD-1 mice received oral doses of vehicle or GKA50 at 20 or 60 mg/kg once daily for four days, and clinical signs, body weight, food consumption, blood chemistry, and hepatic TG were evaluated. In the single oral dose study, dose-dependent decrease in plasma glucose levels and increase in plasma insulin levels were observed. In the four-day repeated dose study, there were no treatment-related changes in clinical signs, body weight, food consumption, or plasma TG levels. In the 60 mg/kg group, a significant increase (P<0.05) in the hepatic TG level was observed. Additionally, the detailed analysis of TG species composition revealed marked increases in TGs mainly composed of 18:1 fatty acids. This study revealed that GKA50 enhanced insulin secretion and hepatic glucose utilization, and increased hepatic TGs, which were mainly composed of 18:1 fatty acids.

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