Unidirectional flux rate of cholesterol and fatty acids into the intestine of rats with drug-induced diabetes mellitus: effect of variations in the effective resistance of the unstirred water layer and the bile acid micelle.

Abstract

A previously validated in vitro technique was used to study the unidirectional flux rate (Jd) of cholesterol and a homologous series of saturated fatty acids (FA) into the jejunum and ileum of rats and alloxan or streptozotocin-induced diabetes mellitus (DM), under conditions of variable resistance of the intestinal unstirred water layer (UWL), and under conditions of varying concentrations of taurodeoxycholic acid (TDC). When the bulk phase was stirred and UWL was low, th Jd of FA 2:0, 4:0, 10:0, and 12:0 were greater in the jejunum and ileum of DM than controls, both 3 and 14 days after alloxan or streptozotocin; the incremental free energy change of transfer of FA was thus higher in DM. The Jd of FA 16:0, 18:0, and cholesterol were increased at 14 but not 3 days after induction of DM; the Jd of cholesterol was higher in DM over a wide range of concentrations of cholesterol, TDC, and both cholesterol and TDC. The Jd of all probe molecules was lower when the bulk phase was unstirred and UWL was high; the Jd of cholesterol but not FA remained greater in DM than in controls. The results suggest that a) the passive permeability of the diabetic intestine to fatty acids is increased in DM but this difference is lost as the animals age; b) the Jd of cholesterol is greater in the jejunum and ileum in DM under conditions of variable concentrations of both cholesterol and bile acids; and c) the bile salt micelle functions in both DM and in controls to solubilize cholesterol and provide the source from which the cholesterol partitions prior to its uptake by the intestinal mucosal membrane.