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Tissue Eng. 2006 Aug;12(8):2105-16.

Glucagon-like peptide-1 differentiation of primate embryonic stem cells into insulin-producing cells.

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  • 1Department of Anatomy and Organ Technology, Institute of Organ Transplants, Reconstructive Medicine and Tissue Engineering, Shinshu University Graduate School of Medicine, Nagano, Japan.


The present study was performed to determine whether glucagon-like peptide-1 (GLP-1) stimulates differentiation of nestin-selected embryonic stem cells into insulin-producing cells. Our experimental strategy began with the production of a highly enriched population of nestin-positive cells from embryoid bodies. These cells differentiated into insulin-producing cells after addition of GLP-1. Islet-like cell clusters (ICCs) formed in inducing culture. These nestin-positive cell-derived ICCs expressed numerous beta-cell lineage genes, including insulin; Glut-2; pancreatic duodenal homebox-1 protein (PDX-1); islet amyloid polypeptide (IAPP); neurogenin 3 (ngn3); and alpha, gamma, and delta cell gene markers. Cells of ICCs showed increased insulin protein expression, glucose-dependent insulin release, and coexpression of insulin and C-peptide. In addition, ICCs were characterized by coexpression of nestin/insulin and nestin/PDX-1. The levels of pancreas-related gene and protein expression and insulin secretion in the GLP-1 group were stronger than those in the normal controls. GLP-1 has been shown to be involved in stimulating the signaling pathways downstream of the transcription factor PDX-1, by increasing its protein and messenger RNA levels. In vivo, ICCs displayed the ability to reverse hyperglycemia in diabetic severe combined immunodeficiency (SCID) mice. We concluded that GLP-1 induced differentiation of nestin-positive progenitor embryonic stem cells into insulin-producing cells, which was achieved by upregulation of PDX-1 expression. This method may have future applications in stem cell therapy of diabetes.

[PubMed - indexed for MEDLINE]
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