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Editor,—I read with interest the recent paper by Schotka et al(Gut1999;44:490–496) which reported that prostaglandin E2 (PGE2) stimulated glucose absorption via the sodium dependent glucose transporter-1 in rat intestine.
The authors suggested that PGE2 raises sodium dependent glucose transporter (SGLT1) and thus increases glucose absorption. However, earlier papers contradicted this theory and we are now in a state of confusion. Kimberg and coworkers1 2 and Klaeveman and colleagues3 have suggested that prostaglandins increase membrane bound adenylate cyclase activity in the small intestinal mucosa, and thus inhibit Na+-K+-ATPase activity of gut mucosa.4 5 Recently, Sundaram and colleagues6 reported that inflamed ileums (excess prostaglandin) express low levels of SGLT1 in rabbits, which indicates that prostaglandin may inhibit SGLT1activity. Furthermore, a decrease in active absorption of glucose due to increased levels of prostaglandins and cytokines has been observed both in patients with severe intestinal inflammation7 and surgical patients.8 9
Can the authors explain an alternative mechanism for their findings?
Editor,—We see no reason for confusion over the acute increase of PGE2-stimulated glucose absorption via SGLT1 in rat small intestine. By using isolated perfused rat small intestine and rat villus tip enterocytes, we showed that PGE2 acutely increased glucose and galactose absorption via SGLT1 with cAMP, raised by the actions of PGE2 receptor subtypes 2 and 4, which served as the second messenger.
As the maximum PGE2 effect was reached after four minutes, the underlying mechanism can only have been stimulation of SGLT1 activity, rather than an increase in the amount of SGLT1 by de novo synthesis. Our findings are concurrent with previous data which showed that forskolin (an adenylate cyclase activator) stimulated a glucose dependent inward current of Na+ 1-1 acutely, in the jejunum of CFTR knockout (cystic fibrosis) mice, and that cAMP increased glucose uptake into brush border membrane vesicles of rat jejunal enterocytes.1-2
Dr Somasundaram now claims that earlier reports contradict this theory. Kimberg, Klaeveman and colleagues showed that prostaglandins stimulated membrane bound adenylate cyclase activity in the small intestine, which is in line with our findings. Mozsik et alshowed that 5'-AMP, cyclic 2',3'-AMP, and cyclic 3',5'-AMP inhibited Na+/K+-ATPase activity in human stomach, indicating that this effect was not specific. Furthermore, Parkinson et al found that Na+/K+-ATPase activity in plasma membrane preparations of rabbit jejunum decreased three hours after cholera toxin treatment; they did not study the direct acute effect of cAMP or PGE2. Sundaram and colleagues, using a rabbit model of chronic ileal inflammation (cells isolated 13–15 days after intragastric inoculation with Eimeria magnaoocytes), concluded that Na+-glucose cotransport reduction was secondary to a decrease in the amount of SGLT1; PGE2 involvement in this chronic alteration was not examined.
Somasundaram et al, who used a rat model of extraintestinal inflammation (six hours after formalin injection into hind leg pad), showed that glucose absorption was impaired in the jejunum, and that this impairment could be prevented by the anti-inflammatory drug, oxyphenbutazone; again PGE2involvement was not investigated. Ohri and colleagues reported that monosaccharides were malabsorbed in coronary artery bypass patients, because of significant hypoperfusion of the intestine; they did not study the involvement of PGE2. Finally, Wickset al concluded that enteral feeding was as effective as total parenteral nutrition in orthotopic liver transplantation; they also did not examine the involvement of PGE2.
In summary, Dr Somasundaram has not presented any evidence that PGE2 lowers SGLT1 activity and acutely or chronically decreases glucose absorption. There is no discrepancy between our findings and any previous study. As PGE2, or any similar hormone or mediator, may have different short term acute and long term chronic actions, and because an appropriate distinction has yet to be made between the state of health and the state of disease, we see no reason for any confusion and no need to provide an alternative mechanism for our findings. We are sure that Dr Somasundaram would be happy to agree.
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