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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred

12 Issues per year


IMPACT FACTOR 2016: 3.273

CiteScore 2016: 3.01

SCImago Journal Rank (SJR) 2016: 1.679
Source Normalized Impact per Paper (SNIP) 2016: 0.800

Online
ISSN
1437-4315
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Volume 387, Issue 7 (Jul 2006)

Issues

A stable analogue of glucose-dependent insulinotropic polypeptide, GIP(LysPAL16), enhances functional differentiation of mouse embryonic stem cells into cells expressing islet-specific genes and hormones

Lamin Marenah
  • School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK
/ Jane T. McCluskey
  • School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK
/ Yasser H.A. Abdel-Wahab
  • School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK
/ Finbarr P.M. O'Harte
  • School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK
/ Neville H. McClenaghan
  • School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK
/ Peter R. Flatt
  • School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK
Published Online: 2006-07-20 | DOI: https://doi.org/10.1515/BC.2006.118

Abstract

Embryonic stem (ES) cells can be differentiated into insulin-producing cells by conditioning the culture media. However, the number of insulin-expressing cells and amount of insulin released is very low. Glucose-dependent insulinotropic polypeptide (GIP) enhances the growth and differentiation of pancreatic β-cells. This study examined the potential of the stable analogue GIP(LysPAL16) to enhance the differentiation of mouse ES cells into insulin-producing cells using a five-stage culturing strategy. Semi-quantitative PCR indicated mRNA expression of islet development markers (nestin, Pdx1, Nkx6.1, Oct4), mature pancreatic β-cell markers (insulin, glucagon, Glut2, Sur1, Kir6.1) and the GIP receptor gene GIP-R in undifferentiated (stage 1) cells, with increasing levels in differentiated stages 4 and 5. IAPP and somatostatin genes were only expressed in differentiated stages. Immunohistochemical studies confirmed the presence of insulin, glucagon, somatostatin and IAPP in differentiated ES cells. After supplementation with GIP(LysPAL16), ES cells at stage 4 released insulin in response to secretagogues and glucose in a concentration-dependent manner, with 35–100% increases in insulin release. Cellular C-peptide content also increased by 45% at stages 4 and 5. We conclude that the stable GIP analogue enhanced differentiation of mouse ES cells towards a phenotype expressing specific β-cell genes and releasing insulin.

Keywords: embryonic stem cells; GIP; insulin-releasing cells

About the article

Corresponding author


Received: December 15, 2005

Accepted: March 20, 2006

Published Online: 2006-07-20

Published in Print: 2006-07-01


Citation Information: Biological Chemistry, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/BC.2006.118.

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