Glucose responsive insulin production from human embryonic germ (EG) cell derivatives

Biochem Biophys Res Commun. 2007 May 11;356(3):587-93. doi: 10.1016/j.bbrc.2007.03.017. Epub 2007 Mar 12.

Abstract

Type 1 diabetes mellitus subjects millions to a daily burden of disease management, life threatening hypoglycemia and long-term complications such as retinopathy, nephropathy, heart disease, and stroke. Cell transplantation therapies providing a glucose-regulated supply of insulin have been implemented clinically, but are limited by safety, efficacy and supply considerations. Stem cells promise a plentiful and flexible source of cells for transplantation therapies. Here, we show that cells derived from human embryonic germ (EG) cells express markers of definitive endoderm, pancreatic and beta-cell development, glucose sensing, and production of mature insulin. These cells integrate functions necessary for glucose responsive regulation of preproinsulin mRNA and expression of insulin C-peptide in vitro. Following transplantation into mice, cells become insulin and C-peptide immunoreactive and produce plasma C-peptide in response to glucose. These findings suggest that EG cell derivatives may eventually serve as a source of insulin producing cells for the treatment of diabetes.

Publication types

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

MeSH terms

  • Animals
  • C-Peptide / metabolism
  • Cells, Cultured
  • Embryonic Stem Cells / drug effects
  • Embryonic Stem Cells / metabolism*
  • Germ Cells / drug effects
  • Germ Cells / metabolism
  • Glucose / pharmacology*
  • Humans
  • Insulin / biosynthesis*
  • Mice
  • Pancreas / embryology
  • Pluripotent Stem Cells / drug effects
  • Pluripotent Stem Cells / metabolism*
  • Proinsulin / biosynthesis
  • Protein Precursors / biosynthesis
  • Stem Cell Transplantation
  • Transcription Factors / biosynthesis
  • Transplantation, Heterologous

Substances

  • C-Peptide
  • Insulin
  • Protein Precursors
  • Transcription Factors
  • preproinsulin
  • Proinsulin
  • Glucose