Characterization of β-cell plasticity mechanisms induced in mice by a transient source of exogenous insulin

Am J Physiol Endocrinol Metab. 2013 Apr 1;304(7):E711-23. doi: 10.1152/ajpendo.00304.2012. Epub 2013 Feb 12.


β-Cell plasticity governs the adjustment of β-cell mass and function to ensure normoglycemia. The study of how β-cell mass is controlled and the identification of alternative sources of β-cells are active fields of research. β-Cell plasticity has been implicated in numerous physiological and pathological conditions. We developed a mice model in which we induced major β-cell mass atrophy by implanting insulin pellets (IPI) for 7 or 10 days. The implants were then removed (IPR) to observe the timing and characteristics of β-cell regeneration in parallel to changes in glycemia. Following IPR, the endocrine mass was reduced by 60% at day 7 and by 75% at day 10, and transient hyperglycemia was observed, which resolved within 1 wk. Five days after IPR, enhanced β-cell proliferation and an increased frequency of small islets were observed in 7-day IPI mice. β-Cell mass was fully restored after an additional 2 days. For the 10-day IPI group, β-cell and endocrine mass were no longer significantly different from those of the control group at 2 wk post-IPR. Furthermore, real-time quantitative PCR analysis of endocrine structures isolated by laser capture microdissection indicated sequentially enhanced expression of the pancreatic transcription factors β(2)/NeuroD and Pdx-1 post-IPR. Thus, our data suggest this mouse model of β-cell plasticity not only relies on replication but also involves enhanced cell differentiation plasticity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Cell Enlargement / drug effects
  • Cell Proliferation
  • Congenital Hyperinsulinism
  • Female
  • Glucose / metabolism
  • Glucose Transporter Type 2 / metabolism
  • Hypoglycemia / chemically induced*
  • Hypoglycemic Agents / pharmacology*
  • Insulin / pharmacology*
  • Insulin-Secreting Cells* / drug effects
  • Insulin-Secreting Cells* / pathology
  • Insulin-Secreting Cells* / physiology
  • Islets of Langerhans* / cytology
  • Islets of Langerhans* / drug effects
  • Islets of Langerhans* / physiology
  • Laser Capture Microdissection
  • Mice
  • Nesidioblastosis
  • Polymerase Chain Reaction
  • RNA, Messenger / analysis*
  • Regeneration / drug effects
  • Regeneration / physiology
  • Time Factors
  • Transcription Factors / metabolism


  • Glucose Transporter Type 2
  • Hypoglycemic Agents
  • Insulin
  • RNA, Messenger
  • Slc2a2 protein, mouse
  • Transcription Factors
  • Glucose