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Safety of Trypsin Inhibitors in the Diet: Effects on the Rat Pancreas of Long-Term Feeding of Soy Flour and Soy Protein Isolate

  • Michael R. Gumbmann
  • William L. Spangler
  • Glenda M. Dugan
  • Joseph J. Rackis
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 199)

Abstract

The effects on the pancreas of chronic dietary exposure to defatted soy flour and soy protein isolate have been studied in two two-year feeding trials in rats. Emphasis was placed on detecting changes that might accompany low levels of dietary trypsin inhibitor (TI) as might be found in edible grade soy products and on studying the influence of protein nutrition. The major pathological findings in the pancreas were nodular hyperplasia (NH), consisting of foci of hyperplastic acinar cells often grossly visible by six months, and the benign neoplastic lesion, acinar adenoma (AA), which developed more slowly.

In the first feeding trial, the objectives were to obtain the dose-response relationship of pancreatic pathology to dietary TI provided by raw and heated soy flour and to study the nutritional interaction of protein level which was varied from 10% to 30% using casein supplementation. Also, the responses to raw and heated soy protein isolate were compared to determine whether the removal of more than 50% of the constituents found in soy flour would alter the development of pancreatic lesions.

In the second trial, the effect of unusually low levels of TI in raw and heat-treated soy protein isolate, prepared through a salt extraction process and fed at 10% and 30% protein in the diet, was investigated.

The incidence of both NH and AA was positively related to the TI content of the diet. The probit transformation of the percent incidence of AA was linearly related to the log of TI/g protein in the diet. A single curve best described the response to 20% and 30% protein, with a slope that was distinctly greater than that for 10% protein. The intersection of the two curves near the TI concentration of edible grade soy flour predicts that protein level in the diet can be expected to have essentially no effect on the incidence of AA when TI activity is in this range. But, for proteins containing greater concentrations of TI, increasing the level of protein in the diet will increase the incidence of pancreatic pathology, while for proteins with quite low levels of TI, increasing the protein in the diet above 10% will have a protective effect. The basis for this interaction between dietary protein and TI is to be found in the nutritional demands for increased protein synthesis accompanying the adaptive response of the pancreas to TI and in the reported influence of low protein levels in sustaining elevated plasma cholecystokinin concentrations.

No significant difference between the response to soy protein isolate, providing 30% protein and graded levels of TI, and that of diets containing soy flour was obtained. This indicates that the non-proteinaceous components removed from soy flour were not factors in the development of pancreatic pathology. The response to the low TI, extracted soy protein isolate (both raw and heated) fed at 30% protein was also equivalent to that of diets containing heated soy flour with casein. However, with 10% protein, the incidence of AA was greater than might be predicted from the probit model, particularly for the raw, low TI soy protein Isolate. Thus, with restricted protein in the diet, proteins of lower quality can be expected to stimulate greater development of pancreatic lesions than would be predicted from TI content alone.

The results of the two feeding studies reported here with defatted soy flour and soy protein isolate indicate that low levels of residual TI equal to those encountered in commercially prepared soy products can be expected to increase the probability of pancreatic adenoma formation in the rat. However, the near exclusive use of the rat as a model has not supplied the breadth of information required to make a useful safety assessment of residual TI in man’s diet.

The appearance of pre-neoplastic and neoplastic lesions of the pancreas in response to chronic dietary exposure of TI in the rat appears to be mediated by the endocrine system of the gastro-intestinal tract which regulates pancreatic function. There is no evidence that TI or other factors in soy are directly involved in the production of pancreatic tumors. Cholecystokinin, a key hormone, can essentially reproduce the early pancreatic alterations brought about by raw soy in the diet, including the development of hyperplasia. Whether the pancreas of the rat is unusually susceptible to the induction of neoplasia when stimulated by the normal regulatory mechanism for pancreatic adaptation to diet remains to be determined. With only limited information as to the generality of the long-term effects of TI on the pancreas in other species, it would be prudent to minimize the intake of dietary factors, such as TI, which may stimulate an undue proliferative response.

Keywords

Trypsin Inhibitor Protein Efficiency Ratio Pancreatic Pathology Pancreas Weight Pancreatic Hypertrophy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Adelson, J. W. and Miller, P. E. (1985). Pancreatic secretion by nonparallel exocytosis: Potential resolution of a long controversy. Science, 228, 993–996.CrossRefGoogle Scholar
  2. Altman, N. H. and Goodman, D. G. (1979). Neoplastic diseases. In: “The Laboratory Rat, Vol. I, Biology and Diseases”, H. J. Baker, J. R. Lindsey, and S. H. Weisbroth, eds., Academic Press, New York, New York, pp. 333–376.Google Scholar
  3. Anagnostides, A. A., Chadwick, V. S., Selden, A. C., Barr, J., and Maton, P. N. (1985). Human pancreatic and biliary responses to physiological concentrations of cholecystokinin octapeptide. Clin. Sci. (Lond.). 69, 259–263.Google Scholar
  4. Andren-Sandberg, A. and Ihse, I. (1983). Regulatory effects on the pancreas of intraduodenal pancreatic juice and trypsin in the Syrian golden hamster. Scand. J. Gastroenterol., 18, 697–706.CrossRefGoogle Scholar
  5. A.O.A.C. (1975). “Official Methods of Analysis”, 12th ed. Assoc. Offic. Anal. Chem., Washington, D.C., p. 857.Google Scholar
  6. Bellili, C., Ormas, P., Cissokho, S., and Beretta, C. (1983). The effects of caerulein on exocrine pancreatic secretion in pigs. Vet. Res. Commun., 6, 43–50.CrossRefGoogle Scholar
  7. Beglinger, C., Fried, M., Whitehouse, I., Jansen, J. B., Lamers, C. B., and Gyr, K. (1985). Pancreatic enzyme response to a liquid meal and to hormonal stimulation. J. Clin. Invest., 75, 1471–1476.CrossRefGoogle Scholar
  8. Bliss, C. I. (1967a). Analysis of fourfold tables. In: “Statistics in Biology, Vol. I”, McGraw-Hill Book Co., New York, New York, pp. 53–91.Google Scholar
  9. Ibid. (1967b). Graphic Tests for Normality, pp. 101–107.Google Scholar
  10. Boorman, G. A. and Eustis, S. L. (1984). Proliferative lesions of the exocrine pancreas in male F344/N rats. Environ. Health Perspectives, 56, 213–217.CrossRefGoogle Scholar
  11. Booth, A. N., Robbins, D. J., Ribelin, W. E., and DeEds, F. (1960). Effect of raw soybean meal and amino acids on pancreatic hypertrophy in rats. Proc. Soc. Exp. Biol. Med., 104, 681–683.Google Scholar
  12. Brand, S. J. and Morgan, R. G. H. (1981). The release of rat intestinal cholecystokinin after oral trypsin inhibitor measured by bio-assay. J. Physiol. (Lond.), 319, 325–343.Google Scholar
  13. Charbonneau, P., Pelletier, G., and Morisset, J. (1982). Development of the pancreas during gestation and lactation in swine. Can. J. Physiol. Pharmacol., 60, 1229–1235.CrossRefGoogle Scholar
  14. Corring, T., Chayvialle, J. A., Simoes-Nunes, C., and Abello, J. (1985). Regulation of pancreatic secretion in the pig by negative feedback and plasma gastrointestinal hormones. Reprod. Nutr. Develop., 25, 439–450.CrossRefGoogle Scholar
  15. Crass, R. A. and Morgan, R. G. H. (1981). Rapid changes in pancreatic DNA, RNA and protein in the rat during pancreatic enlargement and involution. Internat. J. Vit. Nutr. Res., 51, 85–91.Google Scholar
  16. Crass, R. A. and Morgan, R. G. H. (1982). The effect of long-term feeding of soya-bean flour diets on pancreatic growth in the rat. Br. J. Nutr., 47, 119–129.CrossRefGoogle Scholar
  17. Dijkhof, J. and Poort C. (1978). Changes in rat pancreatic protein synthesis after a single feeding with diets containing raw or heated soybeans. J. Nutr., 108, 1222–1228.Google Scholar
  18. Dlugosz, J., Fölsch, U. R., and Creutzfeldt, W. (1982). Effect of intraduodenal inhibition of trypsin on pancreatic exocrine secretion in man. Digestion. 25, 24.Google Scholar
  19. Doell, B. H., Ebden, C. J., and Smith, C. A. (1981). Trypsin inhibitor activity of conventional foods which are part of the British diet and some soya products. Qual. Plant. Plant Foods Hum. Nutr., 31, 139–150.CrossRefGoogle Scholar
  20. Duncan, D. B. (1955). Multiple range and multiple F tests. Biometrics, 11, 1–42.CrossRefGoogle Scholar
  21. Fölsch, U. R., Schafmayer, A., Becker, H. D., and Creutzfeldt, W. (1983). Elevated plasma CCK concentrations in exocrine pancreatic atrophy in the rat. Digestion, 28, 27.Google Scholar
  22. Fölsch, U. R., Wormsley, K. G. (1974). The pancreatic secretion of enzymes in rats treated with soybean diet. Scand. J. Gastroenterol., 9, 679–683.Google Scholar
  23. Food Chem. News. (1983a). Corn oil gavage bioassay results questioned by NTP scientist. February 28, 27–30.Google Scholar
  24. Food Chem. News. (1983b). NTP approves 4-year studies on role of corn oil in gavage tests. October 3, 39–41.Google Scholar
  25. Fraumeni, J. F. (1975). Cancers of the pancreas and biliary tract: Epidemiological considerations. Cancer Res., 35, 3437–3446.Google Scholar
  26. Fried, M., Beglinger, C., Whitehouse, I., and Gyr, K. (1983). Effect of proglumide, a CCK receptor antagonist, on caerulein-induced pancreatic enzyme secretion and plasma PP release. Digestion, 28, 28.Google Scholar
  27. Geratz, J. D. (1968). Growth retardation and pancreatic enlargment in rats due to p-aminobenzamidine. Am. J. Physiol., 214, 595–600.Google Scholar
  28. Geratz, J. D. and Hurt, J. P. (1970). Regulation of pancreatic enzyme levels by trypsin inhibitors. Am. J. Physiol., 219, 705–711.Google Scholar
  29. Giorgi. D., Renaud, W., Bernard, J. P., and Dagorn, J. C. (1985). Regulation of proteolytic enzyme activities and mRNA concentrations in rat pancreas by food content. Biochem. Biophys. Res. Commun., 127, 937–942.CrossRefGoogle Scholar
  30. Goebell, H., Schmitz-Moormann, P., Pfannkuch, U., and Wiechmann, A. (1983). Hypertrophy of the exocrine pancreas: Induction by oral application of the synthetic trypsin inhibitor Foy 305 in rats. Digestion, 28, 31.Google Scholar
  31. Gordis, L. and Gold, E. B. (1984). Epidemiology of pancreatic cancer. World J. Surg., 8, 808–821.CrossRefGoogle Scholar
  32. Green, G. M., Levan, V. H., and Liddle, R. A. (1986). Interaction of dietary protein and trypsin inhibitor on plasma cholecystokinin and pancreatic growth in rats. This volume.Google Scholar
  33. Green, G., Levan, V., and Liddle, R. (1985). Homeostasis of plasma cholecystokinin (CCK) in rats. Fed. Amer. Soc. Exp. Biol. Proc., 44, xii.Google Scholar
  34. Green, G. M. and Lyman, R. L. (1972). Feedback regulation of pancreatic enzyme secretion as a mechanism for trypsin inhibitor-induced hypersecretion in rats. Proc. Soc. Exp. Biol. Med., 140, 6–12.Google Scholar
  35. Green, G. M., Olds, B. A., Matthews, G., and Lyman, R. L. (1973). Protein, as a regulator of pancreatic enzyme secretion in the rat. Proc. Soc. Exp. Biol. Med., 142, 1162–1167.Google Scholar
  36. Grizzle, J. E., Starmer, C. F., and Koch, G. G. (1969). Analysis of categorical data by linear models. Biometrics, 25, 489–504.CrossRefGoogle Scholar
  37. Gumbmann, M. R., Spangler, W. L., Dugan, G. M., Rackis, J. J., and Liener, I. E. (1985). The USDA trypsin inhibitor study. IV. The chronic effects of soy flour and soy protein isolate on the pancreas in rats after two years. Qual. Plant. Plant Foods Hum. Nutr., 35, 275–314.CrossRefGoogle Scholar
  38. Haarstad, H., Winnberg, A., and Petersen, H. (1985). Effects of a cholecystokinin-like peptide on DNA and polyamine synthesis in the rat pancreas. Scand. J. Gastroenterol., 20, 530–538.CrossRefGoogle Scholar
  39. Hamerstrand, G. E., Black, L. T., and Glover, J. D. (1981). Trypsin inhibitors in soy products: Modification of the standard analytical procedure. Cereal Chem., 58, 42–45.Google Scholar
  40. Harper, A. A. and Scratcherd, T. (1979). Physiology. In: “The Exocrine Pancreas”, H. T. Howat and H. Sarles, eds., W. B. Saunders Company Ltd., London, pp 50–85.Google Scholar
  41. Haseman, J. K., Huff, J. E., Rao, G. N., Arnold, J. E., Boorman, G. A., and McConnell, E. E. (1985). Neoplasms observed in untreated and corn oil gavage control groups of F344/N rats and (C57BL/6N × C3H/HeN) F1 (B6C3F1) mice. J. Natl. Cancer Inst., 75, 975–984.Google Scholar
  42. Howatson, A. G. and Carter, D. C. (1985). Pancreatic carcinogenesis-enhancement by cholecystokinin in the hamster-nitrosamine model. Br. J. Cancer, 51, 107–114.CrossRefGoogle Scholar
  43. Jansen, J., Kerstens, P., Welberg, J., Hessels, M., Hafkenscheid J., and Lamers, C. (1983). Physiological plasma concentrations of cholecystokinin stimulate pancreatic enzyme secretion in man. Digestion, 28, 37.Google Scholar
  44. Jensen, R. T., Murphy, R. B., Trampota, M., Schneider, L. H., Jones, S. W., Howard, J. M., and Gardner, J. D. (1985). Proglumide analogs potent cholecystokinin receptor antagonists. Am. J. Physiol., 249, G214–G220.Google Scholar
  45. Kakade, M. L., Hoffa, D. E., and Liener, I. E. (1973). Contribution of trypsin inhibitors to the deleterious effects of unheated soybeans fed to rats. J. Nutr., 103, 1772–1778.Google Scholar
  46. Kakade, M. L., Rackis, J. J., McGhee, J. E., and Puski, G. (1974). Determination of trypsin inhibitor activity of soy products: A collaborative analysis of an improved procedure. Cereal Chem., 51, 376–382.Google Scholar
  47. Kakade, M. L., Simons, N., and Liener, I. E. (1969). An evaluation of natural vs. synthetic substrates for measuring the antitryptic activity of soybean samples. Cereal Chem., 46, 518–526.Google Scholar
  48. Kato, I., Tajima, K., Kuroishi, T., and Tominaga, S. (1985). Latitude and pancreatic cancer. Jpn. J. Clin. Oncol., 15, 403–414.Google Scholar
  49. Konishi, Y., Denda, A., Maruyama, H., Yoshimura, H., Nobuoka, J., and Sunagawa, M. (1980). Pancreatic tumors induced by a single intraperitoneal injection of azaserine in partial pancreatectomized rats. Cancer Lett., 9, 43–46.CrossRefGoogle Scholar
  50. Levison, D. A., Morgan, R. G. H., Brimacombe, J. S., Hopwood, D., Coghill, G., and Wormsley, K. G. (1979). Carcinogenic effects of di(2-hydroxypropyl) nitrosamine (DHPN) in male Wistar rats: Promotion of pancreatic cancer by a raw soya flour diet. Scand. J. Gastroenterol., 14, 217–224.CrossRefGoogle Scholar
  51. Liener, I. E. (1972). Nutritional value of food protein products. in: “Soybeans: Chemistry and Technology”, A. K. Smith and S. J. Circle, eds., AVI Publishing Co., Westport, Connecticut, pp. 203.Google Scholar
  52. Liener, I. E. and Hasdai, A. (1986). The effect of long-term feeding of raw soy flour on the pancreas of the mouse and hamster. This volume.Google Scholar
  53. Liener, I. E. and Kakade, M. L. (1980). Protease inhibitors. In: “Toxic Constituents of Plant Foodstuffs”, I. E. Liener, ed., Academic Press, New York, New York, pp. 7–71.Google Scholar
  54. Liener, I. E., Nitsan, Z., Srisangnam, C., Rackis, J. J., and Gumbmann, M. R. (1985). The USDA trypsin inhibitor study. II. Timed related biochemical changes in the pancreas of rats. Qual. Plant. Plant Foods Hum. Nutr., 35, 243–257.CrossRefGoogle Scholar
  55. Longnecker, D. S., Roebuck, B. D., Yager, J. D., Lilja, H. S., and Siegmund, B. (1981). Pancreatic carcinoma in azaserine-treated rats: Induction, classification and dietary modulation of incidence. Cancer, 47, 1562–1572.CrossRefGoogle Scholar
  56. Longnecker, D. S., Shinozuka, H., and Dekker, A. (1980). Focal acinar cell dysplasia in human pancreas. Cancer, 45, 534–540.CrossRefGoogle Scholar
  57. Lyman, R. L. (1957). The effect of raw soybean meal and trypsin inhibitor diets on the intestinal and pancreatic nitrogen in the rat. J. Nutr., 62, 285–294.Google Scholar
  58. Mainz, D. L., Black, O., and Webster, P. D. (1973). Hormonal control of pancreatic growth. J. Clin. Invest., 52, 2300–2304.CrossRefGoogle Scholar
  59. McGuinness, E. E., Hopwood, D., and Wormsley, K. G. (1982). Further studies of the effects of raw soya flour on the rat pancreas. Scand. J. Gastroenterol., 17, 273–277.CrossRefGoogle Scholar
  60. McGuinness, E. E., Morgan, R. G. H., Levison, D. A., Frape, D. L., Hopwood, D., and Wormsley, K. G. (1980). The effects of long-term feeding of soya flour on the rat pancreas. Scand. J. Gastroenterol., 15, 497–502.CrossRefGoogle Scholar
  61. McGuinness, E. E., Morgan, R. G. H., and Wormsley, K. G. (1984). Effects of soybean flour on the pancreas of rats. Environ. Health Perspectives, 56, 205–212.CrossRefGoogle Scholar
  62. Melmed, R. N. and Bouchier, I. A. D. (1969). A further physiological role for naturally occurring trypsin inhibitors: The evidence for a trophic stimulant of the pancreatic acinar cell. Gut, 10, 973–979.CrossRefGoogle Scholar
  63. Melmed, R. N., El-Aaser, A. A. A., and Holt, S. J. (1976). Hypertrophy and hyperplasia of the neonatal rat exocrine pancreas induced by orally administered soybean trypsin inhibitor. Biochim. Biophys. Acta, 421, 280–288.CrossRefGoogle Scholar
  64. Morgan, R. G. H., Levinson, D. A., Hopwood, D., Saunders, J. H. B., and Wormsley, K. G. (1977). Potentiation of the action of azaserine on the rat pancreas by raw soya bean flour. Cancer Lett., 3, 87–90.CrossRefGoogle Scholar
  65. Oates, P. S. and Morgan, R. G. H. (1982). Pancreatic growth and cell turnover in the rat fed raw soy flour. Am. J. Pathol., 108, 217–224.Google Scholar
  66. Parsa, I., Longnecker, D. S., Scarpelli, D. G., Pour, P., Reddy, J. K., and Lefkowitz, M. (1985). Ductal metaplasia of human exocrine pancreas and its association with carcinoma. Cancer Res., 45, 1285–1290.Google Scholar
  67. Peto, R. (1974). Guidelines on the analysis of tumour rates and death rates in experimental animals. Br. J. Cancer, 29, 101–105.CrossRefGoogle Scholar
  68. Pour, P., Salmasi, S. Z., and Runge, R. G. (1979). Ductular origin of pancreatic cancer and its multiplicity in man comparable to experimentally induced tumors. A preliminary study. Cancer Lett., 6, 89–97.CrossRefGoogle Scholar
  69. Pour, P. M., Sayed, S., and Sayed, G. (1982). Hyperplastic, preneoplastic and neoplastic lesions found in 83 human pancreases. Am. J. Clin. Pathol., 77, 137–152.Google Scholar
  70. Rackis, J. J. (1965). Physiological properties of soybean trypsin inhibitor and their relationship to pancreatic hypertrophy and growth inhibition of rats. Fed. Proc., 24, 1488–1493.Google Scholar
  71. Rackis, J. J. and Gumbmann, M. R. (1981). Protease inhibitors: Physiological properties and nutritional significance. In: “Antinutrients and Natural Toxicants in Foods”, R. L. Ory, ed., Food and Nutrition Press, Inc., Westport, Connecticut, pp. 203–237.Google Scholar
  72. Rackis, J. J., Gumbmann, M. R., and Liener, I. E. (1985). The USDA trypsin inhibitor study. I. Background, objectives, and procedural details. Qual. Plant. Plant Foods Hum. Nutr., 35, 213–242.CrossRefGoogle Scholar
  73. Rackis, J. J., McGhee, J. E., and Booth, A. N. (1975). Biological threshold levels of soybean trypsin inhibitors by rat bioassay. Cereal Chem., 52, 85–92.Google Scholar
  74. Rao, M. S. and Reddy. J. K. (1985). Induction and differentiation of exocrine pancreatic tumors in the rat. Exp. Path., 28, 67–87.CrossRefGoogle Scholar
  75. Roebuck, B. D., Kaplita, P. V., and Macmillan, D. L. (1985). Interaction of dietary fat and soybean isolate (SBI) on azaserine-induced pancreatic carcinogenesis. Qual. Plant. Plant Foods Hum. Nutr., 35, 323–329.CrossRefGoogle Scholar
  76. Roebuck, B. D., Lija, H. S., Curphey, T. J. and Longnecker, D. S. (1980). Pathologic and biochemical effects of azaserine in inbred Wistar/Lewis rats and nonibred CDR −1 mice. J. Nat. Cancer. Inst., 65, 383–389.Google Scholar
  77. Roebuck, B. D., Yager, J. D., Jr., Longnecker, D. S., and Wilpone, S. A. (1981). Promotion by unsaturated fat of azaserine-induced pancreatic carcinogenesis in the rat. Cancer Res., 41, 3961–3966.Google Scholar
  78. Ryan, C. A. and Hass, G. M. (1981). Structural, evolutionary and nutritional properties of proteinase inhibitors from potatoes. In: “Antinutrients and Natural Toxicants in Foods”, R. L. Ory, ed., Food and Nutrition Press, Inc., Westport, Connecticut, pp. 169–185.Google Scholar
  79. SAS Instutite, Inc. (1982a). The GLM procedure. In: “SAS User’s Guide: Statistics, 1982 Edition”, A. A. Ray, ed., SAS Institute Inc., Gary, North Carolina, pp. 139–199.Google Scholar
  80. Ibid. (1982b). The FUNCAT procedure. In: “SAS User’s Guide: Statistics, 1982 Edition”, A. A. Ray, ed., SAS Institute Inc., Gary, North Carolina, pp. 257–285.Google Scholar
  81. Ibid. (1982c). The PROBIT procedure. In: “SAS User’s Guide: Statistics, 1982 Edition”, A. A. Ray, ed., SAS Institute Inc., Gary, North Carolina, pp. 287–292.Google Scholar
  82. Schneeman, B. O. and Lyman, R. L. (1975). Factors involved in the intestinal feedback regulation of pancreatic enzyme secretion in the rat. Proc. Soc. Exp. Biol. Med., 148, 897–903.Google Scholar
  83. Senti, F. R. (1982). Annotated bibliographies on pancreatic changes in experimental animals fed soybeans, processed soybean products, soybean trypsin inhibitor, or cholecystokinin-pancreozymin and antinutritional factors in processed soybean products. Report prepared for Bureau of Foods, Food and Drug Administration, Washington, D. C. Contract no. FDA 223-79-2275, Life Sciences Research Office, Federation of American Societies for Experimental Biology, Bethesda, Maryland.Google Scholar
  84. Snook, J. T. (1969). Factors in whole-egg protein influencing dietary induction of increases in enzyme and RNA levels in rat pancreas. J. Nutr., 97, 286–294.Google Scholar
  85. Solomon, T. E., Grossman, M. I., and Williams, J. A. (1981). Recent advances in pancreatic physiology: Summary of a conference. Fed. Proc., 40, 2105–2110.Google Scholar
  86. Spangler, W. L., Gumbmann, M. R., Liener, I. E., and Rackis, J. J. (1985). The USDA trypsin inhibitor study. III. Sequential development of pancreatic pathology in rats. Qual. Plant. Plant Foods Hum. Nutr., 35, 259–274.CrossRefGoogle Scholar
  87. Stubbs, R. S. and Stabile, B. E. (1985). Role of cholecystokinin in pancreatic exocrine response to intraluminal amino acids and fat. Am. J. Physiol., 248, G347–G352.Google Scholar
  88. Temler, R. S. (1980). Alterations in the pancreas of rats fed on different levels of soya flour and casein. Internat. J. Vit. Nutr. Res., 50, 212–214.Google Scholar
  89. Temler, R. S., Dormond, C. A., Simon, E., and Morel, B. (1984). The effect of feeding soybean trypsin inhibitor and repeated injections of cholecystokinin on rat pancreas. J. Nutr., 114, 1083–1091.Google Scholar
  90. Temler, R. S., Simon, E., Morel, B., and Dormond, C. (1982). Comparison between the effects on rat pancreas of repeated injections of cholecystokinin and soya bean trypsin inhibitor. Digestion, 25, 72.Google Scholar
  91. Toskes, P. P. (1980). Does a negative feedback system for the control of pancreatic exocrine secretion exist and is it of any clinical significance? J. Lab. Clin. Med., 95, 11–12.Google Scholar
  92. Variyam, E. P., Fuller, R. K., Brown, F. M., and Quallich, L. G. (1985). Effect of parenteral amino-acids on human pancreatic exocrine secretion. Dig. Dis. Sci., 30, 541–546.CrossRefGoogle Scholar
  93. Wood, J. G., Dale, W. E., and Solomon, T. E. (1984). Effects of chronic administration of CCK on pancreas of the dog and rat. Gastroenterol., 86, 1302.Google Scholar
  94. Wynder, E. L. (1975). An epidemiological evaluation of the causes of cancer of the pancreas. Cancer Res., 35, 2228–2233.Google Scholar
  95. Yamaguchi, T., Tabata, K., and Johnson, L. R. (1985). Effect of proglumide on rat pancreatic growth. Am. J. Physiol., 249, G294–G298.Google Scholar
  96. Yanatori, Y. and Fujita, T. (1976). Hypertrophy and hyperplasia in the endocrine and exocrine pancreas of rats fed soybean trypsin inhibitor or repeatedly injected with pancreozymin. Arch. Histol. Jap., 39, 67–78.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Michael R. Gumbmann
    • 1
  • William L. Spangler
    • 2
  • Glenda M. Dugan
    • 1
  • Joseph J. Rackis
    • 3
  1. 1.Western Regional Research CenterARS, USDABerkeleyUSA
  2. 2.Veterinary Pathology Consultants, Inc.West SacramentoUSA
  3. 3.PeoriaUSA

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