HIGHLIGHT ARTICLE

JOP. J Pancreas (Online) 2005; 6(3):206-215.

Does the Pancreas Really Produce Much More Lipase than Required for Fat Digestion?

Frédéric Carrière1, Philippe Grandval1,2, Peter C Gregory3, Christophe Renou1,2, Friederike Henniges3, Suntje Sander-Struckmeier3, René Laugier1,2

1Laboratory of Enzymology at Interfaces and Physiology of Lipolysis, CNRS UPR 9025-IBSM. Marseille, France. 2Hepato-Gastroenterology Department, "La Timone" Hospital. Marseille, France. 3Solvay Pharmaceuticals GmbH. Hannover, Germany

Summary

Thirty years ago, it was reported that a linear relationship does not exist between the amounts of human pancreatic lipase secreted in chronic pancreatitis and the degree of steatorrhea, which was considered to appear only after more than 90% of the pancreatic secretory capacity had been lost. From these observations, it was generally thought that the lipolytic potential of the pancreas is much higher than required.

In recent years, however, it has been noted that: 1) the level of inhibition of digestive lipases and gastrointestinal lipolysis by the lipase inhibitor orlistat were almost linearly correlated with the amount of excreted fat; 2) in minipigs with experimentally-induced pancreatic exocrine insufficiency, the amounts of enteric-coated pancreatic extracts needed for restoring fat digestion to normal levels were estimated to be much higher than those usually administered; 3) human pancreatic lipase specific activity on meal triglycerides is 3 orders of magnitude lower than the very high specific activity usually measured under experimental in vitro conditions which are far from physiological conditions; 4) in patients with reduced human pancreatic lipase secretion, gastric lipase plays a significant role in fat digestion.

This last observation might explain the absence of a linear relationship between human pancreatic lipase secretion in chronic pancreatitis and steatorrhea. From the low specific activity displayed by human pancreatic lipase on meal triglycerides, one can better understand why more lipase than expected is needed, why fat digestion lasts for more than a few minutes and, finally, why there is not such an excess secretory capacity for lipase as had been previously thought.

Full text: HTML format   PDF format
  Look up who cited this article

References

  1. DiMagno EP, Go VL, Summerskill WH. Relations between pancreatic enzyme outputs and malabsorption in severe pancreatic insufficiency. N Engl J Med 1973; 288:813-5. [More details]

  2. Heizer WD, Cleaveland CR, Iber FL. Gastric inactivation of pancreatic supplements. Bull John Hopk Hosp 1965; 116:261-70. [More details]

  3. Layer P, Go VL, DiMagno EP. Fate of pancreatic enzymes during small intestinal aboral transit in humans. Am J Physiol 1986; 251:G475-80. [More details]

  4. Layer P, Holtmann G. Pancreatic Enzymes in Chronic Pancreatitis. Int J Pancreatol 1994; 15:1-11. [More details]

  5. DiMagno EP, Malagelada JR, Go VL, Moertel CG. Fate of orally ingested enzymes in pancreatic insufficiency. Comparison of two dosage schedules. N Engl J Med 1977; 296:1318-22. [More details]

  6. Lenaerts C, Beraud N, Castaigne JP. Pancrease gastroresistance: in vitro evaluation of pH-determined dissolution. J Pediatr Gastroenterol Nutr 1988; 7:S18-21. [More details]

  7. Guarner L, Rodriguez R, Guarner F, Malagelada JR. Fate of oral enzymes in pancreatic insufficiency. Gut 1993; 34:708-12. [More details]

  8. Regan PT, Malagelada JR, DiMagno EP, Glanzman SL, Go VL. Comparative effects of antiacids, cimetidine, and enteric coating on the therapeutic response to oral enzymes in severe pancreatic insufficiency. N Engl J Med 1977; 297:854-8. [More details]

  9. Zerega J, Lerner S, Meyer JH. Duodenal instillation of pancreatin does not abolish steatorrhea in patients wiht pancreatic insufficiency. Dig Dis Sci 1988; 33:1245-9. [More details]

  10. Carriere F, Renou C, Ransac S, Lopez V, De Caro J, Ferrato F, et al. Inhibition of gastrointestinal lipolysis by Orlistat during digestion of test meals in healthy volunteers. Am J Physiol Gastrointest Liver Physiol 2001; 281:G16-28. [More details]

  11. Botermans JAM, Hedemann MS, Sörhede-Winzill M, Erlanson-Albertsson C, Svendsen J, Evilevitch L, Pierzynowski SG. The effect of feeding time (day versus night) and feeding frequency on pancreatic exocrine secretion in pigs. J Anim Physiol Anim Nutr 2000; 83:24-35. [More details]

  12. Borovicka J, Schwizer W, Mettraux C, Kreiss C, Remy B, Asal K, et al. Regulation of gastric and pancreatic lipase secretion by CCK and cholinergic mechanisms in humans. Am J Physiol 1997; 273:G374-80. [More details]

  13. Schwizer W, Asal K, Kreiss C, Mettraux C, Borovicka J, Remy B, et al. Role of lipase in the regulation of gastrointestinal function in humans. Am J Physiol 1997; 273:G612-20. [More details]

  14. Carriere F, Renou C, Lopez V, De Caro J, Ferrato F, Lengsfeld H, et al. The specific activities of human digestive lipases measured from the in vivo and in vitro lipolysis of test meals. Gastroenterology 2000; 119:949-60. [More details]

  15. Suzuki A, Mizumoto A, Sarr MG, Dimagno EP. Bacterial lipase and high-fat diets in canine exocrine pancreatic insufficiency: a new therapy of steatorrhea? Gastroenterology 1997; 112:2048-55. [More details]

  16. Meyer JH, Ohashi H, Jehn D, Thomson JB. Size of liver particles emptied from the human stomach. Gastroenterology 1981; 80:1489-96. [More details]

  17. Tabeling R, Gregory PC, Kamphues J. Studies on nutrient digestibilities (pre-caecal and total) in pancreatic duct-ligated pigs and the effects of enzyme substitution. J Anim Physiol Anim Nutr 1999; 82:251-263. [More details]

  18. Lengsfeld H, Beaumier-Gallon G, Chahinian H, De Caro A, Verger R, Laugier R, Carrière F. Physiology of gastrointestinal lipolysis and therapeutical use of lipases and digestive lipase inhibitors. In:Müller G, Petry S eds Lipases and phospholipases in drug developmentWeinheim:Wiley-VCH, 2004:195-229. [More details]

  19. Thirstrup K, Carriere F, Hjorth S, Rasmussen PB, Woldike H, Nielsen PF, Thim L. One-step purification and characterization of human pancreatic lipase expressed in insect cells. FEBS Lett 1993; 327:79-84. [More details]

  20. Carriere F, Barrowman JA, Verger R, Laugier R. Secretion and contribution to lipolysis of gastric and pancreatic lipases during a test meal in humans. Gastroenterology 1993; 105:876-88. [More details]

  21. Roulet M, Weber AM, Paradis Y, Roy CC, Chartrand L, Lasalle R, Morin CL. Gastric emptying and lingual lipase activity in cystic fibrosis. Pediatr Res 1980; 14:1360-2. [More details]

  22. Moreau J, Bouisson M, Balas D, Ravaud A, Stupnik S, Buscail L, Vaysse N, Ribet A. Gastric lipase in alcoholic pancreatitis. Comparison of secretive profiles following pentagastrin stimulation in normal adults and patients with pancreatic insufficiency. Gastroenterology 1990; 99:175-80. [More details]

  23. Carriere F, Grandval P, Renou C, Palomba A, Prieri F, Giallo J, et al. Quantitative study of digestive enzyme secretion and gastrointestinal lipolysis in chronic pancreatitis. Clin Gastroenterol Hepatol 2005; 3:28-38. [More details]

  24. DiMagno EP, Malagelada JR, Go VL. Relationship between alcholism and pancreatic insufficiency. Ann NY Acad Sci 1975; 252:200-7. [More details]

  25. Loser C, Folsch UR. Differential therapy of exocrine pancreatic insufficiency--current aspects and future prospects of substitution therapy with pancreatic enzymes. Z Gastroenterol 1995; 33:715-22. [More details]

  26. Evenepoel P, Claus D, Geypens B, Maes B, Hiele M, Rutgeerts P, Ghoos Y. Evidence for impaired assimilation and increased colonic fermentation of proteins, related to gastric acid suppression therapy. Aliment Pharmacol Ther 1998; 12:1011-19. [More details]

  27. Gregory PC, Tabeling R, Fassmann C, Kamphues J. Therapy of pancreatic exocrine insufficiency: New experimental data. In:Buchler M, Friess H, Uhl W, Malfertheiner P eds Chronic pancreatitis:Novel concepts in biology and therapyBerlin:Blackwell Wissenschafts - Verlag, 2002:445-56. [More details]

  28. Go VL, Hofmann AF, Summerskill WH. Simultaneous measurements of total pancreatic, biliary, and gastric outputs in man using a perfusion technique. Gastroenterology 1970; 58:321-8. [More details]

  29. Johansson C, Lagerlöf HO, Ekelund K, Kulsdom N, Larsson I, Nylind B. Studies of gastrointestinal interactions. III. Determination of gastric secretion and evacuation, biliary and pancreatic secretion, intestinal absorption, intestinal transit time and flow of water in man. Scand J Gastroenterol 1972; 7:489-99. [More details]

  30. Brunner H, Northfield TC, Hofmann AF, Go VL, Summerskill WH. Gastric emptying and secretion of bile acids, cholesterol, and pancreatic enzymes during digestion. Duodenal perfusion studies in healthy subjects. Mayo Clin Proc 1974; 49:851-60. [More details]

  31. Carriere F, Raphel V, Moreau H, Bernadac A, Devaux MA, Grimaud R, et al. Dog gastric lipase: Stimulation of its secretion in vivo and cytolocalization in mucous pit cells. Gastroenterology 1992; 102:1535-45. [More details]

  32. Ville E, Carriere F, Renou C, Laugier R. Physiological study of pH stability and sensitivity to pepsin of human gastric lipase. Digestion 2002; 65:73-81. [More details]

  33. Muller DP, Ghale GK. Stability of pancreatic enzyme activities in duodenal juice after pancreatic stimulation by a test meal or exogenous hormones. Ann Clin Biochem 1982; 19:89-93. [More details]

  34. Kelly DG, Sternby B, DiMagno EP. How to protect human pancreatic enzyme activities in frozen duodenal juice. Gastroenterology 1991; 100:189-195. [More details]

  35. Durie PR, Gaskin KJ, Corey M, Kopelman H, Weizman Z, Forstner GG. Pancreatic function testing in cystic fibrosis. J Pediatr Gastroenterol Nutr 1984; 3:S89-98. [More details]

  36. Ross CA, Sammons HC. Non-pancreatic lipase in children with pancreatic fibrosis. Arch Dis Child 1955; 30:428-431. [More details]

  37. Ross CA. Fat absorption studies in the diagnosis and treatment of pancreatic fibrosis. Arch Dis Child 1955; 30:316-320. [More details]

  38. Lapey A, Kattwinkel J, Di Sant'Agnese PA, Laster L. Steatorrhea and azotorrhea and their relation to growth and nutrition in adolescents and young adults with cystic fibrosis. J Pediatr 1974; 84:328-34. [More details]

  39. Fredrikzon B, Blackberg L. Lingual lipase: an important lipase in the digestion of dietary lipids in cystic fibrosis? Pediatr Res 1980; 14:1387-90. [More details]

  40. Balasubramanian K, Zentler-Munro PL, Batten JC, Northfield TC. Increased intragastric acid-resistant lipase activity and lipolysis in pancreatic steatorrhea due to cystic fibrosis. Pancreas 1992; 7:305-10. [More details]

  41. Meyer JH, Gu YG, Doty JE. Effect of replenished lipase on postcibal absorption of fat in a canine model of pancreatic insufficiency. Pancreas 1994; 9:494-500. [More details]

  42. Layer P, Keller J. Lipase supplementation therapy: standards, alternatives, and perspectives. Pancreas 2003; 26:1-7. [More details]

  43. Opekun AR Jr, Sutton FM Jr, Graham DY. Lack of dose-response with Pancrease MT for the treatment of exocrine pancreatic insufficiency in adults. Aliment Pharmacol Ther 1997; 11:981-986. [More details]

  44. Malesci A, Mariani A, Mezzi G, Bocchia P, Basilico M. New enteric-coated high-lipase pancreatic extract in the treatment of pancreatic steatorrhea. J Clin Gastroenterol 1994; 18:32-5. [More details]

  45. Gullo L. Medical treatment of chronic pancreatitis. Ann Ital Chir 2000; 71:33-7. [More details]

  46. Greenberger NJ. Enzymatic therapy in patients with chronic pancreatitis. Gastroenterol Clin North Am 1999; 28:687-93. [More details]

  47. Gan KH, Heijerman HG, Geus WP, Bakker W, Lamers CB. Comparison of a high lipase pancreatic enzyme extract with a regular pancreatin preparation in adult cystic fibrosis patients. Aliment Pharmacol Ther 1994; 8:603-7. [More details]

  48. van Velzen D, Ball LM, Dezfulian AR, Southgate A, Howard CV. Comparative and experimental pathology of fibrosing colonopathy. Postgrad Med J 1996; 72:S39-48. [More details]

  49. Gaia E, Sambatoro A, De Giuli P, Angeli A. Adult fibrosing colonopathy associated with mesalazine treatment. Am J Gastroenterol 2001; 96:2508-9. [More details]

  50. Bligh EG, Dyer WJ. A rapid method of total lipid extraction and purification. Can J Biochem Physiol 1959; 37:911-917. [More details]

Keywords Exocrine Pancreatic Insufficiency; Pancreatic Function Tests; Pancreatitis; Pancreatitis, Alcoholic

Correspondence: Frédéric Carrière carriere@ibsm.cnrs-mrs.fr; René Laugier: rlaugier@ap-hm.fr