Human β-cell proliferation and intracellular signaling: driving in the dark without a road map

Diabetes. 2012 Sep;61(9):2205-13. doi: 10.2337/db12-0018. Epub 2012 Jun 29.


A major goal in diabetes research is to find ways to enhance the mass and function of insulin secreting β-cells in the endocrine pancreas to prevent and/or delay the onset or even reverse overt diabetes. In this Perspectives in Diabetes article, we highlight the contrast between the relatively large body of information that is available in regard to signaling pathways, proteins, and mechanisms that together provide a road map for efforts to regenerate β-cells in rodents versus the scant information in human β-cells. To reverse the state of ignorance regarding human β-cell signaling, we suggest a series of questions for consideration by the scientific community to construct a human β-cell proliferation road map. The hope is that the knowledge from the new studies will allow the community to move faster towards developing therapeutic approaches to enhance human β-cell mass in the long-term goal of preventing and/or curing type 1 and type 2 diabetes.

Publication types

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

MeSH terms

  • AMP-Activated Protein Kinase Kinases
  • Adaptor Proteins, Signal Transducing / physiology
  • Animals
  • Cell Cycle / drug effects
  • Cell Cycle Proteins
  • Cell Proliferation / drug effects
  • Exenatide
  • Glycogen Synthase Kinase 3 / physiology
  • Humans
  • Insulin Receptor Substrate Proteins / physiology
  • Insulin-Secreting Cells / physiology*
  • Mice
  • Peptides / pharmacology
  • Phosphoproteins / physiology
  • Protein Kinase C / physiology
  • Protein Serine-Threonine Kinases / physiology
  • Ribosomal Protein S6 Kinases / metabolism
  • STAT5 Transcription Factor / physiology
  • Signal Transduction / physiology*
  • TOR Serine-Threonine Kinases / physiology
  • Venoms / pharmacology


  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • EIF4EBP1 protein, human
  • IRS1 protein, human
  • Insulin Receptor Substrate Proteins
  • Peptides
  • Phosphoproteins
  • STAT5 Transcription Factor
  • Venoms
  • Exenatide
  • MTOR protein, human
  • Protein Serine-Threonine Kinases
  • Ribosomal Protein S6 Kinases
  • STK11 protein, human
  • TOR Serine-Threonine Kinases
  • protein kinase C zeta
  • Protein Kinase C
  • Glycogen Synthase Kinase 3
  • AMP-Activated Protein Kinase Kinases