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Department of Medicine -
Section of Digestive Diseases
Research
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Post Doctoral Researchers: |
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Regulation of Na-Nutrient Co-Transport |
PI: |
Uma Sundaram |
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The primary Na absorbing pathways in the mammalian small intestine are Na-glucose co-transport (SGLT-1) and coupled NaCl absorption. The latter is facilitated by the dual operation of Na:H (specifically NHE3) and Cl: HCO3 exchange on the brush border membrane (BBM) of villus cells. How constitutive nitric oxide (cNO), known to regulate many gastrointestinal tract functions, may regulate these important Na absorbing pathways in the normal mammalian small intestine is not well understood.
The goal of this grant is to determine the mechanism of regulation of Na absorption by constitutive nitric oxide in the normal mammalian small intestine.
This study will shed novel insight into the active regulation of and decipher the mechanisms of modulation of essential Na absorbing transport processes by cNO in the normal intestine. It will also provide new insights into the cNO mediated intracellular regulation of these transport processes. Further, the results of these studies will set the stage to decipher the mechanism of regulation of these important Na absorptive pathways in inflammatory bowel disease (IBD). In IBD understanding the regulation of Na absorption is important, as it is known that morbidity of IBD stems from its effect on electrolytes, nutrients and fluid absorption; thus, patients with IBD sustain malabsorption and diarrhea with attendant malnutrition and weight loss. Better understanding of the mechanism of regulation of Na-absorbing transport processes by NO in the normal and chronically inflamed intestine will provide the basis for new and more efficacious treatment modalities for the malabsorption, diarrhea and malnutrition of IBD. |
Regulation of Intestinal Na Absorption |
PI: |
Uma Sundaram |
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The morbidity of inflammatory bowel disease (IBD) stems from its effect on electrolytes, nutrients and fluid absorption; thus, patients with IBD sustain malabsorption and diarrhea with attendant malnutrition and weight loss. It has long been held that once chronic intestinal inflammation has occurred malabsorption and diarrhea are the inevitable results. However, we postulate in this proposal that malabsorption and diarrhea are not the irrevocable end results of chronic intestinal inflammation, but actively regulated processes. This regulation probably occurs by various immune-inflammatory mediators which cause specific alterations of the transporters.
This grant’s purpose it to demonstrate that there is active extracellular regulation of essential Na-nutrient co-transport processes in the chronically inflamed intestine. It will also provide new insights into the exact mechanisms of alteration of these important transporters during chronic enteritis. Better understanding of the mechanism of regulation of Na-dependent nutrient co-transport processes in the chronically inflamed intestine will provide the basis for new and more efficacious treatment modalities for the malabsorption, diarrhea and malnutrition of IBD. |
Recent Publications
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