Correction of hypertriglyceridemia with low high-density lipoprotein cholesterol by the novel compound NO-1886, a lipoprotein lipase-promoting agent, in STZ-induced diabetic rats.
We have previously reported that the novel compound NO-1886 increased lipoprotein lipase (LPL) activity, with resulting elevation of high-density lipoprotein (HDL) cholesterol in normal rats (J Clin Invest 92:411-417, 1993). The aim of this study was to ascertain whether the compound has the same action in diabetes, because hypertriglyceridemia with low HDL cholesterol is an extremely common concomitant condition in diabetes. Streptozotocin-induced diabetic rats showed marked elevation of plasma triglyceride and reduction of HDL cholesterol. Both single and repeated administration of NO-1886 increased postheparin plasma LPL activity, with resulting reduction of plasma triglyceride and elevation of HDL cholesterol. Repeated administration increased the amount of LPL mRNA in adipose tissue and myocardium. The compound had no effects on plasma glucose and insulin levels. Our study indicates that the compound is potentially beneficial for the treatment of hypertriglyceridemia with low HDL cholesterol in diabetes.
Tsutsumi
K
K
New Drug Research Laboratory, Otsuka Pharmaceutical Factory, Incorporated, Tokushima, Japan.
Inoue
Y
Y
Shima
A
A
Murase
T
T
D000273:Adipose Tissue / Q000201:enzymology; D000818:Animals; D001549:Benzamides / Q000627:therapeutic use*; D008076:Cholesterol, HDL / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D004790:Enzyme Induction / Q000187:drug effects; D015870:Gene Expression; D015228:Hypertriglyceridemia / Q000188:drug therapy*; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000201:enzymology; D009943:Organophosphorus Compounds / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar
D001549:Benzamides; D008076:Cholesterol, HDL; D009943:Organophosphorus Compounds; D012333:RNA, Messenger; C082137:4-diethoxyphosphorylmethyl-N-(4-bromo-2-cyanophenyl)benzamide; D008071:Lipoprotein Lipase