Stem Cells Research Today is a free monthly online journal that collates and summarizes the latest research about Stem Cells, including details on research, transplants, therapy, benefits. | ||||||||
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Glucagon-like peptide-1 enhances production of insulin in insulin-producing cells derived from mouse embryonic stem cells.Bai L, Meredith G, Tuch BE Prince of Wales Hospital, The University of New South Wales, Sydney, Australia. Embryonic stem cells (ESCs) can be differentiated into insulin-producing cells by a five-stage procedure involving altering culture conditions and addition of nicotinamide. The amounts of insulin in these cells are lower than those found in pancreatic beta cells. Glucagon-like peptide-1 (GLP-1) induces the differentiation of beta cells from ductal progenitor cells. We examined the possibility of GLP-1, and its long-acting agonist exendin-4, enhancing the differentiation of insulin-producing cells from mouse ESCs (mESCs). A five-stage culturing strategy starting with embryoid bodies (EBs) was used in this study. mRNA for pancreatic duodenal homeobox gene 1 (PDX-1) and neurogenic differentiation (NeuroD) was detected from stage 1, hepatocyte nuclear factor 3 beta (HNF3beta) and insulin 2 from stage 2, Ngn3 and glucose transporter 2 (GLUT2) from stage 3, and insulin 1 and other beta-cell markers, at stages 4-5. Cells at stage 5 secreted C-peptide, being 0.68 +/- 0.01 pmol/10(6) cells per 2 days, and had an immunoreactive insulin content of 13.5 +/- 0.7 pmol/10(6) cells. Addition of GLP-1 (100 nM) and nicotinamide (10 mM) at stage 5 resulted in a 50% and 48% increase in insulin content and C-peptide secretion respectively compared with nicotinamide alone. Glucose-induced insulin secretion was enhanced 4-fold by addition of both growth factors. The GLP-1 receptor was present at all five stages of the culture. Addition of exendin-4 to cells at stage 2 resulted in a 4.9-fold increase in expression of the gene for insulin 1 and a 2-fold increase in insulin content compared with the effect of nicotinamide alone at stage 5. It is concluded that both GLP-1 and exendin-4 enhance the level of expression of insulin in glucose-responsive insulin-producing cells derived from the R1 mESC line. Published 4 August 2005 in J Endocrinol, 186(2): 343-52.
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