β-cell dedifferentiation in diabetes is important, but what is it?

Islets. Sep-Dec 2013;5(5):233-7. doi: 10.4161/isl.27494. Epub 2013 Dec 19.

Abstract

This commentary discusses the concept of β-cell dedifferentiation in diabetes, which is important but not well defined. A broad interpretation is that a state of differentiation has been lost, which means changes in gene expression as well as in structural and functional elements. Thus, a fully mature healthy β cell will have its unique differentiation characteristics, but maturing cells and old β cells will have different patterns of gene expression and might therefore be considered as dedifferentiated. The meaning of dedifferentiation is now being debated because β cells in the diabetic state lose components of their differentiated state, which results in severe dysfunction of insulin secretion. The major cause of this change is thought to be glucose toxicity (glucotoxicity) and that lowering glucose levels with treatment results in some restoration of function. An issue to be discussed is whether dedifferentiated β cells return to a multipotent precursor cell phenotype or whether they follow a different pathway of dedifferentiation.

Keywords: dedifferentiation; diabetes; differentiation; insulin secretion; islets; β cell.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Dedifferentiation / genetics
  • Cell Dedifferentiation / physiology*
  • Cell Differentiation
  • Diabetes Mellitus / pathology
  • Diabetes Mellitus / physiopathology*
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors / genetics
  • Glucose / toxicity*
  • Humans
  • Insulin / metabolism*
  • Insulin Secretion
  • Insulin-Secreting Cells / cytology
  • Insulin-Secreting Cells / pathology
  • Insulin-Secreting Cells / physiology*
  • Multipotent Stem Cells

Substances

  • Forkhead Box Protein O1
  • Forkhead Transcription Factors
  • Foxo1 protein, mouse
  • Insulin
  • Glucose