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Calcineurin mediates pancreatic growth in protease inhibitor-treated mice.

Publication ,  Journal Article
Tashiro, M; Samuelson, LC; Liddle, RA; Williams, JA
Published in: Am J Physiol Gastrointest Liver Physiol
May 2004

CCK acts on pancreatic acinar cells to increase intracellular Ca(2+) leading to secretion of digestive enzymes and, in the long term, pancreatic growth. Calcineurin (CN) is a serine/threonine-specific protein phosphatase activated by Ca(2+) and calmodulin that recently has been shown to participate in the growth regulation of cardiac and skeletal myocytes. We therefore tested the effect of two different CN inhibitors, cyclosporine A (CsA) and FK506, on mouse pancreatic growth induced by oral administration of the synthetic protease inhibitor camostat, a known stimulator of endogenous CCK release. Mice were fed a powdered diet with or without 0.1% camostat. Pancreatic wet weight, protein, and DNA were increased in response to camostat in a time-dependent manner over 10 days in ICR mice but not in CCK-deficient mice. Both CsA (15 mg/kg) and FK506 (3 mg/kg) given twice daily blocked the increase in pancreatic wet weight and protein and DNA content induced by camostat. The increase in plasma CCK induced by camostat was not blocked by CsA or FK506. Camostat feeding also increased the relative amount of CN protein, whereas levels of MAPKs, ERKs, and p38 were not altered. In summary, 1) CCK released by chronic camostat feeding induces pancreatic growth in mice; 2) this growth is blocked by treatment with both CsA and FK506, indicating a role for CN; 3) CCK stimulation also increases CN protein. In conclusion, activation and possibly upregulation of CN may participate in regulation of pancreatic growth by CCK in mice.

Duke Scholars

Published In

Am J Physiol Gastrointest Liver Physiol

DOI

ISSN

0193-1857

Publication Date

May 2004

Volume

286

Issue

5

Start / End Page

G784 / G790

Location

United States

Related Subject Headings

  • Tacrolimus
  • Protease Inhibitors
  • Pancreas
  • Mice, Inbred ICR
  • Mice
  • Male
  • Guanidines
  • Gastroenterology & Hepatology
  • Gabexate
  • Esters
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Tashiro, M., Samuelson, L. C., Liddle, R. A., & Williams, J. A. (2004). Calcineurin mediates pancreatic growth in protease inhibitor-treated mice. Am J Physiol Gastrointest Liver Physiol, 286(5), G784–G790. https://doi.org/10.1152/ajpgi.00446.2003
Tashiro, Mitsuo, Linda C. Samuelson, Rodger A. Liddle, and John A. Williams. “Calcineurin mediates pancreatic growth in protease inhibitor-treated mice.Am J Physiol Gastrointest Liver Physiol 286, no. 5 (May 2004): G784–90. https://doi.org/10.1152/ajpgi.00446.2003.
Tashiro M, Samuelson LC, Liddle RA, Williams JA. Calcineurin mediates pancreatic growth in protease inhibitor-treated mice. Am J Physiol Gastrointest Liver Physiol. 2004 May;286(5):G784–90.
Tashiro, Mitsuo, et al. “Calcineurin mediates pancreatic growth in protease inhibitor-treated mice.Am J Physiol Gastrointest Liver Physiol, vol. 286, no. 5, May 2004, pp. G784–90. Pubmed, doi:10.1152/ajpgi.00446.2003.
Tashiro M, Samuelson LC, Liddle RA, Williams JA. Calcineurin mediates pancreatic growth in protease inhibitor-treated mice. Am J Physiol Gastrointest Liver Physiol. 2004 May;286(5):G784–G790.

Published In

Am J Physiol Gastrointest Liver Physiol

DOI

ISSN

0193-1857

Publication Date

May 2004

Volume

286

Issue

5

Start / End Page

G784 / G790

Location

United States

Related Subject Headings

  • Tacrolimus
  • Protease Inhibitors
  • Pancreas
  • Mice, Inbred ICR
  • Mice
  • Male
  • Guanidines
  • Gastroenterology & Hepatology
  • Gabexate
  • Esters