Changes in the exocrine pancreas secondary to altered small intestinal function in the CF mouse.
The exocrine pancreas of the cystic fibrosis (CF) mouse (cftr(m1UNC)) is only mildly affected compared with the human disease, providing a useful model to study alterations in exocrine function. The CF mouse pancreas has approximately 50% of normal amylase levels and approximately 200% normal Muclin levels, the major sulfated glycoprotein of the pancreas. Protein biosynthetic rates and mRNA levels for amylase were not altered in CF compared with normal mice, and increases in Muclin biosynthesis and mRNA paralleled the increased protein content. Stimulated pancreatic amylase secretion in vitro and in vivo tended to be increased in CF mice but was not statistically significant compared with normal mice. We show for the first time that the CF mouse duodenum is abnormally acidic (normal intestinal pH = 6.47 +/- 0.05; CF intestinal pH = 6.15 +/- 0.07) and hypothesize that this may result in increased signaling to the exocrine pancreas. There were significant increases in CF intestinal mRNA levels for secretin (310% of normal, P < 0.001) and vasoactive intestinal peptide (148% of normal, P < 0.05). Furthermore, CF pancreatic cAMP levels were 147% of normal (P < 0.01). These data suggest that the CF pancreas may be chronically stimulated by cAMP-mediated signals, which in turn may exacerbate protein plugging in the acinar/ductal lumen, believed to be the primary cause of destruction of the pancreas in CF.
De Lisle
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Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, Kansas 66160, USA. rdelisle@kumc.edu
Isom
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Ziemer
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Cotton
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D000681:Amylases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D002135:Calcium-Binding Proteins; D000242:Cyclic AMP / Q000378:metabolism; D003550:Cystic Fibrosis / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins; D006801:Humans; D007150:Immunohistochemistry; D007421:Intestine, Small / Q000378:metabolism*; D051379:Mice; D018181:Mice, Inbred CFTR; D009077:Mucins / Q000235:genetics / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism*; D012633:Secretin / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins; D014660:Vasoactive Intestinal Peptide / Q000235:genetics / Q000378:metabolism
C505032:CFTR protein, human; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; C114202:Dmbt1 protein, mouse; D009077:Mucins; D025521:Tumor Suppressor Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D012633:Secretin; D014660:Vasoactive Intestinal Peptide; D000242:Cyclic AMP; D000681:Amylases