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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2013
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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 |
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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 |
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