Effect of 1-[4-[2-(4-Bromobenzenesulfonamino)ethyl]phenylsulfonyl]-3-(trans-4-methylcyclohexyl)urea (I4), a New Synthetic Sulfonylurea Compound, on Glucose Metabolism in vivo and in vitro

Guan Zhong Wu; Gang Hong; Wen Ping Zhang; Hui Bing Zhang

doi:10.1055/s-0031-1296443

Arzneimittelforschung, Inhaltsverzeichnis

Arzneimittelforschung 2009; 59(11): 550-556
DOI: 10.1055/s-0031-1296443

Antidiabetics

Editio Cantor Verlag Aulendorf (Germany)

Effect of 1-[4-[2-(4-Bromobenzenesulfonamino)ethyl]phenylsulfonyl]-3-(trans-4-methylcyclohexyl)urea (I₄), a New Synthetic Sulfonylurea Compound, on Glucose Metabolism in vivo and in vitro

Autoren

Guan Zhong Wu

¹Department of Pharmacology, China Pharmaceutical University, Nanjing, (P. R. China)
Gang Hong

²Current address: Jiangsu Province Certification Committee for Drugs, Nanjing, (P. R. China)
Wen Ping Zhang

³Current address: Institute of Biochemistry, Zhejiang Sci-Tech University, Hangzhou, (P. R. China)
Hui Bing Zhang

⁴Department of Medical Chemistry, China Pharmaceutical University, Nanjing, (P. R. China)

Abstract

Background:

1-[4-[2-(4-Bromobenzenesulfonamino)ethyl]phenylsulfonyl]-3-(trans-4-methylcyclohexyl)urea (I₄, CAS 865483-06-3), a totally synthetic new sulfonylurea compound, incorporating part of the hypoglycemic structure of glime-piride (CAS 93479-97-1) and having anti-TXA₂ receptor properties, was designed and synthesized. Its hypoglycemic property had not been reported yet.

Aim:

To study the hypoglycemic effects of I₄ and its primary mechanisms of action.

Methods:

A rat model of type 2 diabetes was established by intraperitoneal injection of small doses of streptozntocin combined with high calorie feeding. Normal fasted mice and type 2 diabetic rats were used to assay the hypoglycemic actions of I₄. Blood glucose and immunoreactive insulin concentrations were measured and the effects of I₄ on insulin release from rat isolated pancreatic islets were examined. A liver cell line, Hep G2, was used to examine effects on glucose consumption, glycogen synthesis and glucokinase activity.

Results:

Oral administration of I₄ (1–10 mg/kg) produced a marked, dose-dependent reduction in blood glucose in normal mice and type 2 diabetic rats and improved oral glucose tolerance. Plasma insulin concentrations were increased, and I₄ increased insulin release from rat isolated pancreatic islets and from the isolated perfused rat pancreas. I₄ (1–100 iimol • L⁻¹) also produced an insulin-independent increase in glucose consumption by Hep G2 cells, increased glycogen synthesis and glucokinase activity of these cells. Glimepiride produced similar effects on glucose consumption and glycogen synthesis but did not facilitate glucokinase activity of Hep G2 cells.

Conclusion:

I₄ markedly improved glucose metabolism in normal animals and type 2 diabetic rats, probably by increasing insulin secretion and stimulating hepatic glucose uptake and glycogen synthesis.

Key words

1-[4-[2-(4-Bromobenzenesulfonamino)ethyl]phenylsulfonyl]-3-(trans-4-methyl-cyclohexyl)urea - CAS 865483–06–3 - Glucokinase - I₄, hypoglycemic effect - Pancreatic islets

Volltext

Referenzen

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