Cargando…

Hyperglycemia Slows Embryonic Growth and Suppresses Cell Cycle via Cyclin D1 and p21

In pregnant women, the diabetic condition results in a three- to fivefold increased risk for fetal cardiac malformations as a result of elevated glucose concentrations and the resultant osmotic stress in the developing embryo and fetus. Heart development before septation in the chick embryo was stud...

Descripción completa

Detalles Bibliográficos
Autores principales: Scott-Drechsel, Devon E., Rugonyi, Sandra, Marks, Daniel L., Thornburg, Kent L., Hinds, Monica T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3526024/
https://www.ncbi.nlm.nih.gov/pubmed/23193186
http://dx.doi.org/10.2337/db12-0161
_version_ 1782253491628015616
author Scott-Drechsel, Devon E.
Rugonyi, Sandra
Marks, Daniel L.
Thornburg, Kent L.
Hinds, Monica T.
author_facet Scott-Drechsel, Devon E.
Rugonyi, Sandra
Marks, Daniel L.
Thornburg, Kent L.
Hinds, Monica T.
author_sort Scott-Drechsel, Devon E.
collection PubMed
description In pregnant women, the diabetic condition results in a three- to fivefold increased risk for fetal cardiac malformations as a result of elevated glucose concentrations and the resultant osmotic stress in the developing embryo and fetus. Heart development before septation in the chick embryo was studied under two hyperglycemic conditions. Pulsed hyperglycemia induced by daily administration of glucose during 3 days of development caused daily spikes in plasma glucose concentration. In a second model, sustained hyperglycemia was induced with a single injection of glucose into the yolk on day 0. The sustained model raised the average plasma glucose concentration from 70 mg/dL to 180 mg/dL and led to decreased gene expression of glucose transporter GLUT1. Both models of hyperglycemia reduced embryo size, increased mortality, and delayed development. Within the heart outflow tract, reduced proliferation of myocardial and endocardial cells resulted from the sustained hyperglycemia and hyperosmolarity. The cell cycle inhibitor p21 was significantly increased, whereas cyclin D1, a cell cycle promoter, decreased in sustained hyperglycemia compared with controls. The evidence suggests that hyperglycemia-induced developmental delays are associated with slowed cell cycle progression, leading to reduced cellular proliferation. The suppression of critical developmental steps may underlie the cardiac defects observed during late gestation under hyperglycemic conditions.
format Online
Article
Text
id pubmed-3526024
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher American Diabetes Association
record_format MEDLINE/PubMed
spelling pubmed-35260242014-01-01 Hyperglycemia Slows Embryonic Growth and Suppresses Cell Cycle via Cyclin D1 and p21 Scott-Drechsel, Devon E. Rugonyi, Sandra Marks, Daniel L. Thornburg, Kent L. Hinds, Monica T. Diabetes Pathophysiology In pregnant women, the diabetic condition results in a three- to fivefold increased risk for fetal cardiac malformations as a result of elevated glucose concentrations and the resultant osmotic stress in the developing embryo and fetus. Heart development before septation in the chick embryo was studied under two hyperglycemic conditions. Pulsed hyperglycemia induced by daily administration of glucose during 3 days of development caused daily spikes in plasma glucose concentration. In a second model, sustained hyperglycemia was induced with a single injection of glucose into the yolk on day 0. The sustained model raised the average plasma glucose concentration from 70 mg/dL to 180 mg/dL and led to decreased gene expression of glucose transporter GLUT1. Both models of hyperglycemia reduced embryo size, increased mortality, and delayed development. Within the heart outflow tract, reduced proliferation of myocardial and endocardial cells resulted from the sustained hyperglycemia and hyperosmolarity. The cell cycle inhibitor p21 was significantly increased, whereas cyclin D1, a cell cycle promoter, decreased in sustained hyperglycemia compared with controls. The evidence suggests that hyperglycemia-induced developmental delays are associated with slowed cell cycle progression, leading to reduced cellular proliferation. The suppression of critical developmental steps may underlie the cardiac defects observed during late gestation under hyperglycemic conditions. American Diabetes Association 2013-01 2012-12-13 /pmc/articles/PMC3526024/ /pubmed/23193186 http://dx.doi.org/10.2337/db12-0161 Text en © 2013 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Pathophysiology
Scott-Drechsel, Devon E.
Rugonyi, Sandra
Marks, Daniel L.
Thornburg, Kent L.
Hinds, Monica T.
Hyperglycemia Slows Embryonic Growth and Suppresses Cell Cycle via Cyclin D1 and p21
title Hyperglycemia Slows Embryonic Growth and Suppresses Cell Cycle via Cyclin D1 and p21
title_full Hyperglycemia Slows Embryonic Growth and Suppresses Cell Cycle via Cyclin D1 and p21
title_fullStr Hyperglycemia Slows Embryonic Growth and Suppresses Cell Cycle via Cyclin D1 and p21
title_full_unstemmed Hyperglycemia Slows Embryonic Growth and Suppresses Cell Cycle via Cyclin D1 and p21
title_short Hyperglycemia Slows Embryonic Growth and Suppresses Cell Cycle via Cyclin D1 and p21
title_sort hyperglycemia slows embryonic growth and suppresses cell cycle via cyclin d1 and p21
topic Pathophysiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3526024/
https://www.ncbi.nlm.nih.gov/pubmed/23193186
http://dx.doi.org/10.2337/db12-0161
work_keys_str_mv AT scottdrechseldevone hyperglycemiaslowsembryonicgrowthandsuppressescellcycleviacyclind1andp21
AT rugonyisandra hyperglycemiaslowsembryonicgrowthandsuppressescellcycleviacyclind1andp21
AT marksdaniell hyperglycemiaslowsembryonicgrowthandsuppressescellcycleviacyclind1andp21
AT thornburgkentl hyperglycemiaslowsembryonicgrowthandsuppressescellcycleviacyclind1andp21
AT hindsmonicat hyperglycemiaslowsembryonicgrowthandsuppressescellcycleviacyclind1andp21