ADAPTATION OF INTESTINAL NUTRIENT TRANSPORT IN HEALTH AND DISEASE .1.

Why is it important to understand the mechanisms controlling intestina l adaptation? There are two major answers to this question. Firstly, i n establishing the cellular and molecular events associated with intes tinal adaptation, we will formulate a general framework that may be ap plied to the understanding of adaptation of other cell membranes. For example, alterations in the synthesis of glucose carriers and their su bsequent insertion into membranes may alter sugar entry across the int estinal brush border membrane (BBM) using the sodium-dependent D-gluco se transporter, SGLT1, or the BBM sodium-independent facultative fruct ose transporter, GLUTS, and may alter facilitated sugar exit across th e basolateral membrane (BLM) using GLUT2. The precise role of transcri ptional and translational processes in the up- or down-regulation of s ugar transport requires further definition. Alterations in enterocyte microsomal lipid metabolic enzyme expression occurring during the cour se of intestinal adaptation will direct the synthesis of lipids destin ed for trafficking to the BBM and BLM domains of the enterocyte. This will subsequently alter the passive permeability properties of these m embranes and ultimately influence lipid absorption. Therefore, establi shing the physiological, cellular and molecular mechanisms of adaptati on in the intestine will define principles that may be applied to othe r epithelia. Secondly, enterocyte membrane adaptation is subject to di etary modification, and these may; be exploited as a means to enhance a beneficial or to reduce a detrimental aspect of the intestinal adapt ive 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. Therefo re, 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 centerpie ce for future investigation that would focus on disease prevention, as well as on the development of better therapeutic strategies to preven t the development or to treat the complications of conditions such as diabetes mellitus, obesity, hyperlipidemia and inflammatory bowel dise ases. This review deals with the physiology of glucose transport with specific emphasis on transporters of the brush border membrane (BBM) a nd the basolateral membrane (BLM). On the BBM the sodium (Na)/glucose transporters (SGLT1 and SGLT2), the Na-independent transporter (GLUTS) , and on the BLM the hexose transporter (GLUT2) are discussed. The mol ecular biology of these transporters is also reviewed.