Increases in intestinal glucose absorption and hepatic glucose uptake elicited by luminal but not vascular glutamine in the jointly perfused small intestine and liver of the rat

Abstract

1. Previous studies have shown that an arterial-to-portal glucose concentration gradient may be an important signal for insulin-dependent net hepatic glucose uptake. It is not known whether intestinal factors also contribute to the regulation of hepatic glucose utilization. This problem was studied in a newly developed model which allows luminal perfusion of the small intestine via the pyloric sphincter and a combined vascular perfusion of the small intestine via the gastroduodenal artery and superior mesenteric artery, and of the liver via the hepatic artery and portal vein. 2. In both the presence and the absence of 1 mM-glutamine in the vascular perfusate, only about 7% of a luminal bolus of 5500 mumol (1 g) of glucose was absorbed by the small intestine, and nothing was taken up by the liver. 3. With small doses of 75-380 mumol (11-55 mg) of luminal glutamine, but not with 300 mumol of alanine, the intestinal absorption of the luminal glucose bolus was increased almost linearly from 7% to a maximum of 40% and the hepatic uptake from 0% to a maximum of 22%. 4. The increase of hepatic glucose uptake caused by luminal glutamine was only observed when the glucose load was applied into the intestinal lumen, rather than into the superior mesenteric artery. 5. The relative hepatic glucose uptake (uptake/portal supply) was enhanced from 0% to 55% with an increase in portal supply by luminal glutamine, whereas with a similar range of portal glucose supply the relative hepatic uptake by the isolated liver, perfused simultaneously via the hepatic artery and portal vein, was slightly decreased, from 20% to 15%. 6. Addition of various amounts of portal glutamine and/or alterations in the Na+ content of the portal perfusate failed to mimic the luminal glutamine-dependent activation of hepatic glucose uptake. Therefore the luminal-glutamine-elicited activation of hepatic glucose uptake was apparently not caused by a simple increase in the portal-arterial glucose gradient, by glutamine itself or by Na(+)-dependent alterations in hepatic cell volume. The results suggest that luminal glutamine caused not only an increase in intestinal glucose absorption by unknown mechanisms but also the generation of one or more humoral or nervous 'hepatotropic' signals in the small intestine which enhanced the hepatic uptake of absorbed glucose.

Enhancing bowel adaptation in short bowel syndrome

“…Glutamine is an important fuel for rapidly dividing cells, including those of the small intestinal mucosa. It has been suggested that glutamine accelerates hyperplasia following resection and enhances intestinal glucose and sodium absorption [68][69][70][71][72]. However, Vanderhoof et al [73] were unable to demonstrate a trophic effect with the addition of 5% glutamine to a chow diet following resection in the rat.…”

A New Treatment for Patients with Short-Bowel Syndrome Growth Hormone, Glutamine, and a Modified Diet

“…Providing parenteral feedings that contained this amino acid supported mucosal growth under a variety of conditions,2' including mucosal hypertrophy that occurred after extensive small-bowel resection.22 Other studies have documented improved bowel function, including absorption, when L-glutamine was provided by parenteral23 and/or enteral feedings. 24 Second, both animal and human studies have demonstrated that growth hormone, now available in recombinant form, stimulates intestinal growth25 and enhances transport ofnutrients across the small bowel. 26 Although we observed few significant clinical effects when these agents were administered alone, under the conditions of our study, enhanced absorption was observed when the agents were given together.…”

Luminal polyamines upregulate transmural glucose transport in the rat small intestine

“…Therefore, it is not possible that the action of the polyamines on glucose absorption is mediated via other hormones or the de-novo synthesis of SGLT1, because the response time is so short. Gardmann et al 21 reported that luminal glutamine upregulated glucose uptake from the small intestine within 2 min, although they did not measure SGLT1 protein. 21 Stümpel et al 7 indicated that an intra-arterial injection of glucagon 37 immediately stimulated glucose absorption in the rat intestine, and concluded that it exerted its actions via SGLT1.…”

“…Gardmann et al 21 reported that luminal glutamine upregulated glucose uptake from the small intestine within 2 min, although they did not measure SGLT1 protein. 21 Stümpel et al 7 indicated that an intra-arterial injection of glucagon 37 immediately stimulated glucose absorption in the rat intestine, and concluded that it exerted its actions via SGLT1. Therefore, a mechanism exists to activate glucose transporters rapidly.…”