The many lives of Myc in the pancreatic β-cell

J Biol Chem. 2021 Jan-Jun:296:100122. doi: 10.1074/jbc.REV120.011149. Epub 2020 Dec 2.


Diabetes results from insufficient numbers of functional pancreatic β-cells. Thus, increasing the number of available functional β-cells ex vivo for transplantation, or regenerating them in situ in diabetic patients, is a major focus of diabetes research. The transcription factor, Myc, discovered decades ago lies at the nexus of most, if not all, known proliferative pathways. Based on this, many studies in the 1990s and early 2000s explored the potential of harnessing Myc expression to expand β-cells for diabetes treatment. Nearly all these studies in β-cells used pathophysiological or supraphysiological levels of Myc and reported enhanced β-cell death, dedifferentiation, or the formation of insulinomas if cooverexpressed with Bcl-xL, an inhibitor of apoptosis. This obviously reduced the enthusiasm for Myc as a therapeutic target for β-cell regeneration. However, recent studies indicate that "gentle" induction of Myc expression enhances β-cell replication without induction of cell death or loss of insulin secretion, suggesting that appropriate levels of Myc could have therapeutic potential for β-cell regeneration. Furthermore, although it has been known for decades that Myc is induced by glucose in β-cells, very little is known about how this essential anabolic transcription factor perceives and responds to nutrients and increased insulin demand in vivo. Here we summarize the previous and recent knowledge of Myc in the β-cell, its potential for β-cell regeneration, and its physiological importance for neonatal and adaptive β-cell expansion.

Keywords: DNA methylation; Myc; adaptation; aging; diabetes; glucose; pancreatic β-cell; proliferation.

Publication types

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

MeSH terms

  • Animals
  • Cell Proliferation
  • Cellular Senescence
  • Glucose / metabolism
  • Humans
  • Hyperglycemia / metabolism
  • Insulin-Secreting Cells / cytology
  • Insulin-Secreting Cells / metabolism*
  • Promoter Regions, Genetic
  • Protein Conformation
  • Proto-Oncogene Proteins c-myc / chemistry
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Proto-Oncogene Proteins c-myc / physiology
  • Structure-Activity Relationship


  • Proto-Oncogene Proteins c-myc
  • Glucose