Uptake of Bile Acids Into Rat Intestine: Effect of Diabetes Mellitus

Abstract

Diabetes mellitus is associated with the enhanced uptake of several nutrients. The purpose of this study was to use an established in vitro technique to examine the uptake of bile acids into jejunum, ileum, and colon of control (CON) and streptozotocin-diabetic rats (DM). When the bulk phase was stirred to reduce the effective thickness of the unstirred layer, the ileal uptake of 1.5–15 mM cholic (C), glycocholic (GC), taurocholic (TC), chenodeoxycholic (CDC), glycochenodeoxycholic (GCDC), and deoxycholic (DC) acid was similar in CON and DM. The relative values of the maximal transport rates were CDC > GC > GCDC > C > TC = DC, and similar relative values were observed for the Michaelis constants (Km). The values of and Km for each bile acid were similar in CON and in DM. In CON and at pH 7.4 an inverse linear relationship was noted between the number of hydrogen bonds in the bile acids and the natural logarithm of the permeability coefficient (Pd) times the square root of the molecular weight of the bile acid. This slope reflected the incremental change in free energy, δΔFw ← I, associated with the uptake of bile acids; the value of δΔFw ← I was similar for jejunum, ileum, and colon of CON, but was lower in jejunum of DM than CON. Thus, DM is associated with a greater relative permeability of the jejunum but not the ileum or the colon to a series of bile acids. At pH 4.2, the uptake of the bile acids was much greater than at pH 7.4, and the relative ratio of the Pd's of the bile acids was different than the values at pH 7.4, and varied between jejunum, ileum, and colon in CON and DM. Thus, diabetes has a variable effect on the uptake of bile acids, and this effect depends on the bile acid, site, and pH. The kinetics of the ileal active transport system, like those of passive uptake, are dependent upon molecular structure. The finding of different values for of the bile acids suggests that there may be more than one ileal carrier for bile acids, but the properties of these carriers are unaffected by StreptOZOtOCin diabetes in the rat.