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Am J Physiol Gastrointest Liver Physiol (February 5, 2003). doi:10.1152/ajpgi.00402.2002
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Submitted on September 18, 2002
Accepted on January 22, 2003

Modulation of intestinal protein synthesis and protease mRNA by luminal and systemic nutrients

Olasunkanmi A.J. Adegoke1, Michael I. McBurney1, Susan E. Samuels2, and Vickie E. Baracos1*

1 Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada
2 Department of Food, Nutrition and Health, The University of British Columbia, Vancouver, British Columbia, Canada

* To whom correspondence should be addressed. E-mail: vickie.baracos{at}ualberta.ca.

Route of nutrient supply is important in regulation of intestinal protein metabolism, as total parenteral nutrition, in comparison with enteral feeding, leads to profound atrophy. The participation of protein synthesis (Ks) and degradation in regulation of gut protein balance and their possible modulation by specific nutrients are the focus of our work. We developed an in situ experimental system that allows controlled exposure of intestinal mucosa to nutrients systemically, luminally or both. We examined the effects of systemic glucose and amino acid (AA) infusion in overnight-fasted piglets. Jejunal segments within each piglet were simultaneously luminally perfused with solutions containing various amino acids or glucose. Intravenous infusion of glucose increased mucosal Ks by 16% (P < 0.05), while intravenous infusion of AA had no effect on Ks. Systemic glucose infusion had no effect on mRNA levels for components of the ubiquitin-proteasome proteolytic pathway. However, levels of these mRNA were reduced by intravenous or luminal AA supply. This effect was greatest (-50%) when highest tissue concentrations of amino acids were achieved by the simultaneous infusion of AA by both routes (P < 0.05). Our findings suggest that the modulation of protein balance in the intestine in response to nutrients is only in part attributable to anabolic stimulation of protein synthesis initiated by the systemic appearance of glucose, but that a fall in protein degradation is also a likely contributor. Amino acids appear to be a key factor required to reduce expression of genes connected with proteolysis.




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