Pancreatic regenerating protein I in chronic pancreatitis and aging: Implications for new therapeutic approaches to diabetes

Martin Bluth, Cathy M. Mueller, Joelle Pierre, Gordon Callender, Emad Kandil, Domenico Viterbo, Sophia L. Fu, Akira Sugawara, Hiroshi Okamoto, Michael E. Zenilman

Research output: Contribution to journalArticle

Abstract

OBJECTIVES:: We investigated the relationship of pancreatic regenerating protein (reg) in models of acinar cell atrophy and aging, and the effect of reg I protein replacement on glucose tolerance. METHODS:: Rats underwent pancreatic duct ligation (PDL) and were followed through 12 months. Aging rats were studied at 12 and 20 months. Intraperitoneal glucose tolerance tests (IPGTTs) were performed, pancreatic reg I, reg I receptor, insulin gene expression, and reg I protein levels were measured. Pancreatic duct ligation and aged animals were treated with exogenous reg I protein and assessed for glucose metabolism. RESULTS:: After PDL, chronic atrophic pancreatitis developed, with a progressive loss of acinar cells and pancreatic reg I. During aging, a similar depression of reg I gene expression was also noted. The reg I levels correlated with pancreatic insulin levels. Twelve months after PDL, IPGTT results were abnormal, which were significantly improved by administration of reg I protein. Aged animals demonstrated depressed IPGTT, which marginally improved after reg I administration. Anti-reg antibody administration to young rats depressed IPGTT to elderly levels. CONCLUSIONS:: Depletion of the acinar product reg I is associated with the pathogenesis of impaired glucose tolerance of pancreatitis-associated diabetes and aging, and replacement therapy could be useful in these patients. Reg I is an acinar cell product, which affects islet function.

Original languageEnglish (US)
Pages (from-to)386-395
Number of pages10
JournalPancreas
Volume37
Issue number4
DOIs
Publication statusPublished - Nov 2008
Externally publishedYes

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Keywords

  • Aging
  • Diabetes
  • Ductal ligation
  • Pancreas
  • Reg, therapy
  • Regeneration protein

ASJC Scopus subject areas

  • Hepatology
  • Internal Medicine
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Bluth, M., Mueller, C. M., Pierre, J., Callender, G., Kandil, E., Viterbo, D., ... Zenilman, M. E. (2008). Pancreatic regenerating protein I in chronic pancreatitis and aging: Implications for new therapeutic approaches to diabetes. Pancreas, 37(4), 386-395. https://doi.org/10.1097/MPA.0b013e31817f7893