T. Yokoyama et al., EFFECTS OF KRN4884, A NOVEL PYRIDINECARBOXAMIDINE TYPE K-ATP CHANNEL OPENER, ON SERUM TRIGLYCERIDE LEVELS IN RATS, British Journal of Pharmacology, 120(8), 1997, pp. 1471-1476
1 The effects of KRN4884, a novel pyridinecarboxamidine type K-ATP cha
nnel opener, on serum triglyceride levels were investigated in Sprague
-Dawley rats. 2 Oral administration of KRN4884 (3 mg kg(-1)) for 10 da
ys caused a significant reduction in serum triglyceride levels, which
was comparable to that of clofibrate (160 mg kg(-1)). Reduction in ser
um triglyceride levels by KRN4884 and clofibrate were accompanied by a
reduction in triglyceride levels both in chylomicron and in very low
density lipoprotein. KRN4884 treatment did not affect serum concentrat
ions of total cholesterol and phospholipid, but did increase free fatt
y acid levels. Clofibrate reduced total cholesterol, phospholipid and
free fatty acid levels. 3 Administration of clofibrate significantly d
ecreased triglyceride secretion rate as measured by the Triton WR-1339
injection procedure, while KRN4884 did not. 4 Rats receiving KRN4884
exhibited an increase in lipoprotein lipase (LPL) activity both in adi
pose tissue and in skeletal muscle. There was an inverse correlation b
etween serum triglyceride levels and tissue LPL activities. KRN4884 di
d not change hepatic triglyceride lipase (HTGL) activity. Clofibrate a
ffected neither LPL nor HTGL activities. 5 It is concluded that admini
stration of KRN4884 results in reduced serum triglyceride levels which
may be due to the enhancement of LPL activity in peripheral tissues.