Streptozotocin-induced expression of Ngn3 and Pax4 in neonatal rat pancreatic α-cells

World J Gastroenterol. 2011 Jun 21;17(23):2812-20. doi: 10.3748/wjg.v17.i23.2812.


Aim: To investigate the mechanism behind β-cell regeneration in neonatal rat pancreas treated with streptozotocin (STZ).

Methods: Neonatal Sprague Dawley rats were intraperitoneally injected with 70 mg/kg STZ. Body weight, pancreas weight and blood glucose were recorded every two days after the treatment. To identify the expression and location of transcription factors in the rat pancreas, double immunofluorescent staining was performed using antibodies to specific cell markers and transcription factors.

Results: Expression of Neurogenin 3 (Ngn3), a marker for endocrine precursor cells, was observed by immunofluorescence in a few β-cells and many α-cells. The expression reached a peak 12 d after treatment. Pax4, a transcription factor that lies downstream of Ngn3 and plays an important role in β-cell differentiation, was also expressed in the α-cells of STZ-treated rats. We did not observe significant changes in Nkx6.1, which is essential for β-cell maturation in the treated rats.

Conclusion: α-cells dedifferentiated into endocrine precursor cells and acquired the ability to dedifferentiate in the neonatal rat pancreas after STZ treatment.

Keywords: Dedifferentiation; Endocrine precursor cells; Pancreatic remodeling; Streptozotocin; Transcription factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Cell Dedifferentiation / drug effects
  • Diabetes Mellitus, Experimental / metabolism
  • Female
  • Glucagon-Secreting Cells / cytology
  • Glucagon-Secreting Cells / drug effects*
  • Glucagon-Secreting Cells / physiology*
  • Homeodomain Proteins / metabolism*
  • Insulin / metabolism
  • Insulin-Secreting Cells / cytology
  • Insulin-Secreting Cells / metabolism
  • Nerve Tissue Proteins / metabolism*
  • Paired Box Transcription Factors / metabolism*
  • Pregnancy
  • Rats
  • Rats, Sprague-Dawley
  • Regeneration / drug effects*
  • Stem Cells / cytology
  • Stem Cells / physiology
  • Streptozocin / pharmacology*


  • Basic Helix-Loop-Helix Transcription Factors
  • Homeodomain Proteins
  • Insulin
  • Nerve Tissue Proteins
  • Neurog3 protein, rat
  • Paired Box Transcription Factors
  • Pax4 protein, rat
  • Streptozocin