Effect of oral clofibrate administration on intestinal 3- O-methyl glucose absorption in rat and chick

Abstract

1. 1. These studies were undertaken to determine the effect of clofibrate ( p-chlorophenoxyisobutyrate, CPIB) on intestinal glucose absorption and the possible relationship to its hypolipidemic action in rat and chick. The effect of CPIB and diabetes on intestinal mucosal C-AMP concentration as well as the role of C-AMP in intestinal glucose absorption was also determined in rat. 2. 2. CPIB treatment decreased intestinal 3- O-methyl glucose absorption when expressed as absolute transport (1.37 ± 0.27 vs 3.47 ± 0.27 μmoles/g mucosa) or as serosal: mucosal ratio (1.28 ± 0.05 vs 1.62 ± 0.04) for the CPIB treated and control rats respectively. In the chick CPIB had no effect. 3. 3. In vitro addition of dibutyryl C-AMP significantly increased glucose transport in sacs prepared from control rats (1.96 ± 0.14 vs 3.23 ± 0.38 μmoles/g respectively) but not from CPIB treated rats. 4. 4. The mucosal C-AMP contents for the control, diabetic and CPIB treated rats were 248.2 ± 24.3, 428.5 ± 65.2 and 214.0 ± 23.9 pmole/g mucosa respectively. 5. 5. After an oral glucose load both serum glucose and insulin levels were higher during the first 20 min for the control rats compared to CPIB treated rats. 6. 6. Serum triglycerides were significantly lower in the CPIB treated rats compared to control rats and decreased in both groups following oral glucose load. 7. 7. Whereas CPIB increased liver weight in the rat (6.34 ± 0.20 vs 4.13 ± 0.09 g/100 g body wt.), it had no effect in the chick (2.57 ± 0.04 vs 2.56 ± 0.14 g/100 g body wt.) for the CPIB treated and controls respectively. 8. 8. Although CPIB decreased glucose transport only in the rat, it had a hypolipidemic effect in both the rat and the chick. 9. 9. Our results suggest that either intestinal glucose absorption is not involved in the hypolipidemic effect or there are species differences in the mechanism of action of CPIB.