Exocrine pancreas glutamate secretion help to sustain enterocyte nutritional needs under protein restriction.

Glutamine (G1n) is the most concentrated amino acid in blood and considered conditionally essential. Its requirement is increased during physiological stress, such as malnutrition or illness, despite its production by muscle and other organs. In the malnourished state. G1n has been suggested to have a trophic effect on the exocrine pancreas and small intestine. However, the G1n transport capacity, the functional relationship of these two organs, and the potential role of the G1n-glutamate (G1u) cycle are unknown. We observed that pancreatic acinar cells express lower levels of G1u than G1n transporters. Consistent with this expression pattern, the rate of G1u influx into acinar cells was approximately sixfold lower than that of G1n. During protein restriction, acinar cell glutaminase expression was increased and G1n accumulation was maintained. Moreover, Glu secretion by acinar cells into pancreatic juice and thus into the lumen of the small intestine was maintained. In the intestinal lumen, Glu absorption was preserved and Glu dehydrogenase expression was augmented, potentially providing the substrates for increasing energy production via the TCA cycle. Our findings suggest that one mechanism by which Gin exerts a positive effect on exocrine pancreas and small intestine involves the Gin metabolism in acinar cells and the secretion of Glu into the small intestine lumen. The exocrine pancreas acinar cells not only avidly accumulate G1n but metabolize Gin to generate energy and to synthesize Glu for secretion in the pancreatic juice. Secreted Glu is suggested to play an important role during malnourishmenl in sustaining small intestinal homeostasis. NEW & NOTEWORTHY Glutamine (Gin) has been suggested to have a trophic effect on exocrine pancreas and small intestine in malnourished states, but the mechanism is unknown. In this study, we suggest that this trophic effect derives from an interorgan relationship between exocrine pancreas and small intestine for Gln-glutamate (Glu) utilization involving the uptake and metabolism of Gln in acinar ceils and secretion of Glu into the lumen of the small intestine.