, Volume 42, Issue 3, pp 453-469

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

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Abstract

Why is it important to understand the mechanismscontrolling intestinal adaptation? There are two majoranswers to this question. Firstly, in establishing thecellular and molecular events associated with intestinal adaptation, we will formulate ageneral framework that may be applied to theunderstanding of adaptation of other cell membranes. Forexample, alterations in the synthesis of glucosecarriers and their subsequent insertion into membranesmay alter sugar entry across the intestinal brush bordermembrane (BBM) using the sodium-dependent D-glucosetransporter, SGLT1, or the BBM sodium-independent facultative fructose transporter, GLUT5, andmay alter facilitated sugar exit across the basolateralmembrane (BLM) using GLUT2. The precise role oftranscriptional and translational processes in the up- or down-regulation of sugar transport requiresfurther definition. Alterations in enterocyte microsomallipid metabolic enzyme expression occurring during thecourse of intestinal adaptation will direct the synthesis of lipids destined fortrafficking to the BBM and BLM domains of theenterocyte. This will subsequently alter the passivepermeability properties of these membranes andultimately influence lipid absorption. Therefore, establishing thephysiological, cellular and molecular mechanisms ofadaptation in the intestine will define principles thatmay be applied to other epithelia. Secondly, enterocyte membrane adaptation is subject to dietarymodification, and these may be exploited as a means toenhance a beneficial or to reduce a detrimental aspectof the intestinal adaptive process in disease states. Alterations in membrane function occur inassociation with changes in dietary lipids, and theseare observed in a variety of cells and tissues includinglymphocytes, testes, liver, adipocytes, nerve tissue, nuclear envelope and mitochondria. Therefore,the elucidation of the mechanisms of intestinaladaptation and the manner whereby dietary manipulationmodulates these processes affords the future possibility of dietary engineering aimed at using food asa therapeutic agent. It is hoped this approach will formthe centerpiece for future investigation that wouldfocus on disease prevention, as well as on the development of better therapeutic strategies toprevent the development or to treat the complications ofconditions such as diabetes mellitus, obesity,hyperlipidemia and inflammatory bowel diseases. This review deals with the physiology of glucosetransport with specific emphasis on transporters of thebrush border membrane (BBM) and the basolateral membrane(BLM). On the BBM the sodium (Na)/glucose transporters (SGLT1 and SGLT2), the Naindependenttransporter (GLUT5), and on the BLM the hexosetransporter (GLUT2) are discussed. The molecular biologyof these transporters is also reviewed.