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| Unprocessed proinsulin promotes cell survival during neurulation in the chick embryo |
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| Author(s): Hernandez-Sanchez C, Rubio E, Serna J, de la Rosa EJ, de Pablo F |
| Source: DIABETES Volume: 51 Issue: 3 Pages: 770-777 Published: MAR 2002 |
| Times Cited: 19 References: 50 |
| Abstract: We have chosen a vertebrate model accessible during neurulation, the chick, for analysis of endogenous insulin signaling and its contribution to early embryonic cell survival. Unlike rodents, humans and chickens have a single preproinsulin gene, facilitating its prepancreatic expression characterization. We show that in vivo interference with embryonic insulin signaling using antiense oligonucleotides against the insulin receptor increases apoptosis during neurulation. In contrast, high glucose administration does not increase the level of apoptosis in culture or in vivo. Exogenous insulin and, remarkably, proinsulin achieve similar survival protective effects at 10(-8) mol/l. The low abundant preproinsulin mRNA from the prepancreatic embryo is translated to a protein that remains as unprocessed proinsulin. This concurs with the absence of prohormone convertase 2 (PC2) in the embryo, whereas PC2 is present later in embryonic pancreas. A C-peptide specific antibody stains proinsulin-containing neuroepithelial cells of the chick embryo in early neurulation, as well as other cells in mesoderm- and endoderm-derived structures in the 2.5-day embryo. We have determined by 5'-RACE (rapid amplification of cDNA ends), and confirmed by RNase protection assay, that prepancreatic and pancreatic proinsulin mRNA differ in their first exon, suggesting differential transcriptional regulation. All these data support the role of endogenous proinsulin in cell survival in the chick embryo during important pathophysiologic periods of early development. |
| Document Type: Article |
| Language: English |
| Reprint Address: de Pablo, F (reprint author), CSIC, Ctr Invest Biol, Grp Growth Factors Vertebrate Dev, Velazquez 144, E-28006 Madrid, Spain |
Addresses:
1. CSIC, Ctr Invest Biol, Grp Growth Factors Vertebrate Dev, E-28006 Madrid, Spain |
| Publisher: AMER DIABETES ASSOC, 1660 DUKE ST, ALEXANDRIA, VA 22314 USA |
| Subject Category: Endocrinology & Metabolism |
| IDS Number: 527CD |
| ISSN: 0012-1797 |
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