Experimental diabetes and intestinal barriers to absorption

Abstract

The unstirred water layer (UWL) and the brush-border membrane represent the major barriers to intestinal absorption. Enhanced uptake of several nutrients has been described in diabetes mellitus, and this study was undertaken in the rat to define whether these absorptive changes are due to alterations in the characteristics of these barriers. Using in vitro techniques the effective resistance of UWL was measured with lauryl alcohol, the rate of uptake (Jd) of which is limited by diffusion across the UWL. At all rates of stirring of the bulk phase, the effective resistance of UWL was less in diabetic than control rats. The Jd of a homologous series of saturated fatty acids (4:0-18:0) and cholesterol was higher than disks of intestine of diabetic than control intestine; this enhanced uptake of lipid could not be demonstrated using intestinal biopsies. The change in incremental free energy of transfer of fatty acid uptake into disks was higher in diabetic than control animals after correction for UWL effects. After correction for UWL, the Michaelis constant for Jd of D-glucose was similar in diabetic and control jejunum, and the greater Jd of glucose in diabetics was due to a higher maximal transport rate (Jmd) and a higher passive permeability coefficient. It is concluded that the enhanced uptake of glucose, fatty acids, fatty alcohols, and cholesterol into diabetic intestine is due to a reduction in the effective resistance of the UWL, an increase in the passive permeability properties of the membrane, and a rise in the Jmd for D-glucose.