Adaptation of Intestinal Nutrient Transport in Health and Disease (Part I)

A.B.R. Thomson, G. Wild

Why is it important to understand the mechanisms controlling intestinal adaptation? There are two major answers to this question. Firstly, in establishing the cellular and molecular events associated with intestinal adaptation, we will formulate a general framework that may be applied to the understanding of adaptation of other cell membranes. For example, alterations in the synthesis of glucose carriers and their subsequent insertion into membranes may alter sugar entry across the intestinal brush border membrane (BBM) using the sodium-dependent D-glucose transporter, SGLT1, or the BBM sodium-independent facultative fructose transporter, GLUT5, and may alter facilitated sugar exit across the basolateral membrane (BLM) using GLUT2. The precise role of transcriptional and translational processes in the up- or down-regulation of sugar transport requires further definition. Alterations in enterocyte microsomal lipid metabolic enzyme expression occurring during the course of intestinal adaptation will direct the synthesis of lipids destined for trafficking to the BBM and BLM domains of the enterocyte. This will subsequently alter the passive permeability properties of these membranes and ultimately influence lipid absorption. Therefore, establishing the physiological, cellular and molecular mechanisms of adaptation in the intestine will define principles that may be applied to other epithelia. Secondly, enterocyte membrane adaptation is subject to dietary modification, and these may be exploited as a means to enhance a beneficial or to reduce a detrimental aspect of the intestinal adaptive process in disease states. Alterations in membrane function occur in association with changes in dietary lipids, and these are observed in a variety of cells and tissues including lymphocytes, testes, liver, adipocytes, nerve tissue, nuclear envelope and mitochondria. Therefore, the elucidation of the mechanisms of intestinal adaptation and the manner whereby dietary manipulation modulates these processes affords the future possibility of dietary engineering aimed at using food as a therapeutic agent. It is hoped this approach will form the centerpiece for future investigation that would focus on disease prevention, as well as on the development of better therapeutic strategies to prevent the development or to treat the complications of conditions such as diabetes mellitus, obesity, hyperlipidemia and inflammatory bowel diseases. This review deals with the physiology of glucose transport with specific emphasis on transporters of the brush border membrane (BBM) and the basolateral membrane (BLM). On the BBM the sodium (Na)/glucose transporters (SGLT1 and SGLT2), the Na-independent transporter (GLUT5), and on the BLM the hexose transporter (GLUT2) are discussed. The molecular biology of these transporters is also reviewed.