Effects of KRN4884, a novel pyridinecarboxamidine type KATP channel opener, on serum triglyceride levels in rats

1. The effects of KRN4884, a novel pyridinecarboxamidine type KATP channel opener, on serum triglyceride levels were investigated in Sprague-Dawley rats. 2. Oral administration of KRN4884 (3 mg kg-1) for 10 days caused a significant reduction in serum triglyceride levels, which was comparable to that of clofibrate (160 mg kg-1). Reduction in serum 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 concentrations of total Cholesterol and phospholipid, but did increase free fatty acid levels. Clofibrate reduced total Cholesterol, phospholipid and free fatty acid levels. 3. Administration of clofibrate significantly decreased 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 adipose tissue and in skeletal muscle. There was an inverse correlation between serum triglyceride levels and tissue LPL activities. KRN4884 did not change hepatic triglyceride Lipase (HTGL) activity. Clofibrate affected neither LPL nor HTGL activities. 5. It is concluded that administration of KRN4884 results in reduced serum triglyceride levels which may be due to the enhancement of LPL activity in peripheral tissues.