Effects of the lipoprotein lipase activator NO-1886 as a suppressor agent of atherosclerosis in aorta of mild diabetic rabbits.

Abstract

The synthetic compound NO-1886 ([4-(4-bromo-2-cyano-phenylcarbamoyl)-benzyl]-phosphonic acid diethyl ester, CAS 133208-93-2) is a lipoprotein lipase activator which decreases plasma triglycerides and elevates high-density lipoprotein cholesterol (HDL-C) levels. However, the effects of NO-1886 on plasma glucose level and atherosclerosis in diabetes are not clear. The aim of this study was to ascertain whether the compound lowers plasma glucose and suppresses atherosclerosis in New Zealand White rabbits with high fat/high sucrose-induced mild diabetes. High fat/high sucrose feeding increased plasma total cholesterol, triglyceride and glucose levels and decreased HDL-C levels resulting in atherosclerosis in the aorta. Administration of NO-1886 to the rabbits resulted in decreased plasma total cholesterol, triglyceride and glucose levels and increased HDL-C levels after 20 weeks of treatment. Furthermore, NO-1886 provided protection against the development of atherosclerosis in the aorta. These data indicate that NO-1886 not only ameliorates the lipid disorder, but also lowers plasma glucose levels and suppresses atherosclerosis in the aorta of diabetic rabbits.