Lack of Effect of Cerulein on Pancreatic Growth of Rats Fed a Low-Protein Diet

Abstract

The effect of dietary protein deficiency and protein concentration of the diet on the pancreatic trophic response to a CCK analogue (cerulein) were studied. Rats were fed for 14 days with semipurified diets containing 5, 30, or 60% casein. During the final 4 days, they received 2 Kglkg cerulein or gelatin vehicle subcutaneously three times/day, and the effects on pancreatic weight and pancreatic content of protein, RNA, DNA, amylase, and chymotrypsin were determined. Cerulein failed to increase significantly any pancreatic parameter in rats fed 5% casein, while stimulating significant increases in almost all parameters in rats fed 30 and 60% casein diets. In the absence of cerulein treatment, increases in dietary protein levels caused progressive increases in all pancreatic growth parameters with the exception of amylase. In the presence of cerulein, increases in dietary protein concentrations caused progressive increases in pancreatic growth parameters (except amylase), which were maximal at 30% casein concentration of the diet for most parameters. The results confirm that pancreatic growth is stimulated by increasing protein concentration of the diet and indicate that a low protein diet, acting through a deficiency of dietary nitrogen and essential amino acids, limits the pancreatic trophic response to CCK or analogues. These results explain the failure of trypsin inhibitors to stimulate pancreatic growth in rats fed low levels of dietary protein. Key Words: Exocrine pancreatic growth-CholecystokininProtein deficiency-Dietary protein.Exocrine pancreatic growth is stimulated by the gastrointestinal hormone cholecystokinin (CCK) and by high-protein diets and diets containing trypsin inhibitors (1,2). These diets are strong releasers of CCK in the rat, which may account for their effect on pancreatic growth (3,4). The role of absorbed essential amino acids and nitrogen in nutritional support of pancreatic growth stimulated by trophic hormones is largely unexplored. Rats fed raw soybean diets developed pancreatic hypertrophy, but the degree of pancreatic growth was greatly increased by supplementation of the raw soybean diet with essential amino acids (5). This suggests that inadequacy of dietary essential amino acids and nitrogen (for synthesis of nonessential amino acids) may limit the pancreatic growth response to endogenous CCK.We previously reported that soybean trypsin inhibitor (1% of diet) stimulated pancreatic growth in rats fed diets containing 10% and 20% casein for 7 182 CERULEIN AND PANCREATIC GROWTH 183 days, but not in rats fed diets containing 5% casein, in spite of a large increase in plasma CCK levels in the latter group (6). We proposed that this was because of a deficiency of available dietary nitrogen and essential amino acids needed to support a pancreatic growth response to the endogenous trophic stimulus CCK. To test this hypothesis, we determined the effect of dietary protein concentration on the pancreatic growth response to chronic treatment with cerulein, a CCK analogue. Rats were adapte...

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

“…Furthermore, evidence that trypsinogen expression is greatly diminished when nitrogen is provided in the form of amino acids may be particularly relevant in the treatment of pancreatitis, where trypsin activation may play a pivotal role in the onset of the disease (34). In rodents, the pancreas is less responsive to cerulein in stimulating growth and digestive enzyme synthesis on a low-protein diet compared with a normal or high-protein diet (14), and protein-free diets are protective against experimental pancreatitis (12). Furthermore, we recently demonstrated (23) that rats given TPN were protected against secretagogue-induced pancreatitis.…”

Experimental pancreatic hyperplasia and neoplasia: effects of dietary and surgical manipulation

“…Since the growth-stimulating properties of raw soya flour on the pancreas are greatly increased by supplementing the diet with essential amino acids (Booth et al, 1960) (Green et al, 1991).…”

CCK-, secretin-, and cholinergic-independent pancreatic fluid hypersecretion in protease inhibitor-treated rats

“…Cell proliferation requires energy and substrates for protein synthesis, and depletion of either can slow or prevent replication. Indeed, recent studies have demonstrated that a low-protein diet or the absence of food in the gastrointestinal tract decreases the trophic effects of both exogenous and endogenous CCK on the rat pancreas (4,9). Thus oral intake of adequate protein is important to induce the full effect of PI.…”