Pancreatic function in CCK-deficient mice: adaptation to dietary protein does not require CCK

Am J Physiol. 1999 May;276(5):G1302-9. doi: 10.1152/ajpgi.1999.276.5.G1302.


A CCK-deficient mouse mutant generated by gene targeting in embryonic stem cells was analyzed to determine the importance of CCK for growth and function of the exocrine pancreas and for pancreatic adaptation to dietary changes. RIAs confirmed the absence of CCK in mutant mice and demonstrated that tissue concentrations of the related peptide gastrin were normal. CCK-deficient mice are viable and fertile and exhibit normal body weight. Pancreas weight and cellular morphology appeared normal, although pancreatic amylase content was elevated in CCK-deficient mice. We found that a high-protein diet increased pancreatic weight, protein, DNA, and chymotrypsinogen content similarly in CCK-deficient and wild-type mice. This result demonstrates that CCK is not required for protein-induced pancreatic hypertrophy and increased proteolytic enzyme content. This is a novel finding, since CCK has been considered the primary mediator of dietary protein-induced changes in the pancreas. Altered somatostatin concentrations in brain and duodenum of CCK-deficient mice suggest that other regulatory pathways are modified to compensate for the CCK deficiency.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptation, Physiological
  • Amylases / analysis
  • Animals
  • Cholecystokinin / deficiency*
  • Cholecystokinin / genetics
  • Cholecystokinin / physiology*
  • Chymotrypsinogen / analysis
  • Dietary Proteins / administration & dosage*
  • Digestive System / chemistry
  • Female
  • Gastrins / analysis
  • Gene Targeting
  • Male
  • Mice
  • Mutagenesis
  • Organ Size
  • Pancreas / cytology
  • Pancreas / enzymology
  • Pancreas / physiology*
  • RNA, Messenger / analysis
  • Receptor, Cholecystokinin A
  • Receptors, Cholecystokinin / genetics
  • Somatostatin / analysis


  • Dietary Proteins
  • Gastrins
  • RNA, Messenger
  • Receptor, Cholecystokinin A
  • Receptors, Cholecystokinin
  • Somatostatin
  • Cholecystokinin
  • Chymotrypsinogen
  • Amylases