Islet hypertrophy following pancreatic disruption of Smad4 signaling

Diane M. Simeone, Lizhi Zhang, Mary K. Treutelaar, Lanjing Zhang, Kathleen Graziano, Craig D. Logsdon, Charles F. Burant

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

To investigate the role of transforming growth factor (TGF)-β family signaling in the adult pancreas, a transgenic mouse (E-dnSmad4) was created that expresses a dominant-negative Smad4 protein driven by a fragment of the elastase promoter. Although E-dnSmad4 mice have normal growth, pancreas weight, and pancreatic exocrine and ductal histology, beginning at 4-6 wk of age, E-dnSmad4 mice show an age-dependent increase in the size of islets. In parallel, an expanded population of replicating cells expressing the E-dnSmad4 transgene is found in the stroma between the enlarged islets and pancreatic ducts. Despite the marked enlargement, E-dnSmad4 islets contain normal ratios and spatial organization of endocrine cell subtypes and have normal glucose homeostasis. Replication of cells derived from primary duct cultures of wild-type mice, but not E-dnSmad4 mice, was inhibited by the addition of TGF-β family proteins, demonstrating a cell-autonomous effect of the transgene. These data show that, in the adult pancreas, TGF-β family signaling plays a role in islet size by regulating the growth of a pluripotent progenitor cell residing in the periductal stroma of the pancreas.

Original languageEnglish (US)
Pages (from-to)E1305-E1316
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume291
Issue number6
DOIs
StatePublished - 2006

Keywords

  • Diabetes
  • Elastase
  • Islet growth
  • Nestin
  • Transforming growth factor-β
  • Transgenic mice

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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  • Cite this

    Simeone, D. M., Zhang, L., Treutelaar, M. K., Zhang, L., Graziano, K., Logsdon, C. D., & Burant, C. F. (2006). Islet hypertrophy following pancreatic disruption of Smad4 signaling. American Journal of Physiology - Endocrinology and Metabolism, 291(6), E1305-E1316. https://doi.org/10.1152/ajpendo.00561.2005