The potential role of glucokinase activator SHP289-04 in anti-diabetes and hepatic protection

European Journal of Pharmacology
Lei LeiZhufang Shen

Abstract

Glucokinase was glucose sensor in hepatocytes and islet beta cells. It not only promoted glucose metabolism, but also advanced glucose-stimulated insulin secretion. Glucokinase activators had been reported as one kind of new potential drugs for treatment of type 2 diabetes. Compound 6-(5-(3-fluorobenzyloxy)-2-ethoxybenzamido) pyridine-3-carboxylic acid (SHP289-04) was found to increase glucokinase activity effectively by our lab. In order to demonstrate its effect of anti-diabetes, in vitro, human liver carcinoma cell line HepG2 was used to glucose consumption test, and pancreatic cell line NIT-1 was used to assess insulin secretion in response to different concentration of glucose (5 mmol/l and 20 mmol/l). Type 2 diabetes model KKAy mice were chose to evaluate the pharmacodynamics of SHP289-04 in vivo. In hepatocytes, SHP289-04 could accelerate glucose consuming. In NIT cell line, it promoted glucose-stimulated insulin secretion at the 20 mmol/l of glucose. Moreover, it normalized oral glucose tolerance test and down-regulated blood lipid level in KKAy mice. At the same time, it ameliorated function of islets and accelerated the ratio of beta cell/alpha cell mass, and also alleviated the fatty liver of KKAy mice. Therefore, SH...Continue Reading

Citations

Dec 14, 2018·Current Medicinal Chemistry·Sara N GarciaM Matilde Marques
Nov 2, 2019·Current Drug Targets·Ping WuHao Fang
Oct 30, 2021·Chemical Biology & Drug Design·Ramasamy ThilagavathiChelliah Selvam

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