Although it has become increasingly clear that intestinal absorption is regulated by both the luminal contents and by a variety of hormonal and neural mediators, these mechanisms have not. been well characterized. Previous studies from this laboratory have employed neurovascularly intact, canine jejunal segments (Thiry Vella loops), transplanted out of continuity with the rest of the gastrointestinal tract, to examine such adaptation. Not only are these segments capable of short. term regulation with an immediate proabsorptive increase in fluid, and electrolyte transport following a meal but there is evidence of long term adaptation, ie. intestinal atrophy, as well. This atrophy occurs even with normal neural and hormonal mediators present. This renewal application proposes to extend these observations and to examine the mechanisms of this adaptation. In addition, through human studies, we hope to relate these observations to clinical conditions where bowel atrophy plays a role in functional adaptation. To this end, the experiments described in this proposal have the following specific aims: 1. To further characterize both short and long term adaptation in the isolated, neurovascularly intact loop model. 2. To identify the luminal, neuroendocrine and cellular mechanisms of this adaptation. 3. To test the hypothesis that these adaptive responses represent alterations in absorption by sodium-glucose cotransport, the major jejunal sodium transporter, and to determine the responsible mechanisms. 4. To begin to examine this adaptation in a human in vivo model of intestinal transport. The results of these studies should find application in a variety of clinical settings including intestinal recovery after total parenteral nutrition, the return of function after the ileo-anal pullthrough operation and small bowel transplantation. We anticipate that these findings may be applied therapeutically to alter (stimulate or inhibit) the adaptive response.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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Surgery and Bioengineering Study Section (SB)
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University of California Los Angeles
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Los Angeles
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