Intravenous or luminal amino acids are insufficient to maintain pancreatic growth and digestive enzyme expression in the absence of intact dietary protein

Abstract

We previously reported that rats receiving total parenteral nutrition (TPN) undergo significant pancreatic atrophy characterized by reduced total protein and digestive enzyme expression due to a lack of intestinal stimulation by nutrients (Baumler MD, Nelson DW, Ney DM, Groblewski GE. Am J Physiol Gastrointest Liver Physiol 292: G857-G866, 2007). Essentially identical results were recently reported in mice fed protein-free diets (Crozier SJ, D'Alecy LG, Ernst SA, Ginsburg LE, Williams JA. Gastroenterology 137: 1093-1101, 2009), provoking the question of whether reductions in pancreatic protein and digestive enzyme expression could be prevented by providing amino acids orally or by intravenous (IV) infusion while maintaining intestinal stimulation with fat and carbohydrate. Controlled studies were conducted in rats with IV catheters including orally fed/saline infusion or TPN-fed control rats compared with rats fed a protein-free diet, oral amino acid, or IV amino acid feeding, all with oral carbohydrate and fat. Interestingly, neither oral nor IV amino acids were sufficient to prevent the pancreatic atrophy seen for TPN controls or protein-free diets. Oral and IV amino acids partially attenuated the 75-90% reductions in pancreatic amylase and trypsinogen expression; however, values remained 50% lower than orally fed control rats. Lipase expression was more modestly reduced by a lack of dietary protein but did respond to IV amino acids. In comparison, chymotrypsinogen expression was induced nearly twofold in TPN animals but was not altered in other experimental groups compared with oral control animals. In contrast to pancreas, protein-free diets had no detectable effects on jejunal mucosal villus height, total mass, protein, DNA, or sucrase activity. These data underscore that, in the rat, intact dietary protein is essential in maintaining pancreatic growth and digestive enzyme adaptation but has surprisingly little effect on small intestinal mucosa.

Protein deficiency alters impact of intestinal nematode infection on intestinal, visceral and lymphoid organ histopathology in lactating mice

“…In addition to the lower relative liver mass in PD mice, relative pancreas mass was also reduced by protein deficiency, consistent with the well-established sensitivity of the exocrine pancreas to dietary components including protein (Brannon, 1990; Baumler et al 2010). The composite pancreatitis score in all groups was driven predominantly by leucocyte infiltration, which tended to be higher in infected dams, possibly due to infection-associated systemic inflammatory signals.…”

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

“…Maintaining Glu secretion during protein restriction. During total parenteral nutrition and protein-deficient diet, the exocrine pancreatic volume and the synthesis of digestive enzymes are diminished (3,18). However, despite the reduction of pancreas volume and protein synthesis, the secretion of free Glu was unchanged in our animals receiving a proteindeficient diet.…”

“…Exocrine pancreas deficiency develops as a result of an insufficient amount or quality of protein arriving in the digestive tract, causing changes to the synthesis and secretion of digestive enzymes and a reduction in organ volume (7,18,29,45). Even when adequate caloric content is supplied intravenously (total parenteral nutrition), morphological and functional alterations in the exocrine pancreas and small intestine are observed (3,70). In these patients, further supplementing parenteral diets with glutamine (Gln) has a positive effect partially restoring the normal homeostasis of small intestine and pancreas (2,24,31).…”

Objective evaluation of blood flow in the small-intestinal villous: quantification of findings from dynamic endoscopy with concomitant narrow-band imaging

“…Baumler et al found that rats receiving total parenteral nutrition (TPN) can develop jejunum atrophy due to lack of nutrient irritation in the bowel 14 . In another report, the same group suggested that oral and intravenous administration of an amino acid formulation improved decreased pancreatic function, but had no effects on atrophy of the jejunal mucous membrane in rats given TPN 15 . These reports suggest that, for villous function in the small intestine, explosive irritation by pancreatic enzymes may play an important role, rather than nutrient irritation of amino acids, and this may be the reason why SDOV reflects PEF.…”