Synergistic Endocrine Induction by GLP-1 and TGF-?? in the Developing Pancreas

Abstract

We conclude that TGF-beta isoforms have a specific synergistic role with GLP-1 pathway signaling in early pancreatic development, toward endocrine differentiation and away from acinar differentiation.

The Role of Incretins in Glucose Homeostasis and Diabetes Treatment

“…GLP-1R activation of those cells also affects transforming growth factor-β signaling pathways, resulting in reduced Smad activity that is conducive to endocrine phenotypes (Yew et al, 2004, 2005; Tei et al, 2005). AR42J cells, even without GLP-1R activation, have the potential to be converted into endocrine (Mashima et al, 1996) or exocrine cells (Christophe, 1994) but are negative for islet hormones and their transcripts under usual culture conditions (Zhou et al, 1999b).…”

Neurogenin3: A master regulator of pancreatic islet differentiation and regeneration

“…Treatment with GLP-1 has been shown to enhance b-cell differentiation in several experimental systems, suggesting additional roles for proglucagon-derived peptides in pancreas development. [34][35][36][37] It is also shown that transgenic overexpression of Pancreatic Polypeptide (PP) in the developing pancreas example, Ngn3 binds directly to the promoters of the b-cellspecific transcription factors b2/NeuroD and Pax4 to promote the differentiation of progenitor cells into the b cell lineage. 24,25 Ngn3 expression is extinguished coincident with the expression of the endocrine hormones that define the endocrine lineages, for example the insulin expression in b cells (Fig.…”

Generating pancreatic β-cells from embryonic stem cells by manipulating signaling pathways

“…It was reported some time ago that TGFb1 (TGFB1) enhanced the development of endocrine cells from mouse pancreatic fetal cells, with a more pronounced increase in b-and PP-cells (Sanvito et al 1994), and this effect was subsequently reproduced by Tei et al (2005). Another study showed that TGFb2 (TGFB2) induced differentiation of mESCs into Pdx1-expressing endodermal cells (Shiraki et al 2005), but several other growth factors from this family, including TGFa and TGFb1, did not have any significant effect on promoting Pdx1 expression.…”