Hyperglycemia slows embryonic growth and suppresses cell cycle via cyclin D1 and p21.
Hyperglycemia slows embryonic growth and suppresses cell cycle via cyclin D1 and p21.
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作者：
Scott-Drechsel DE;Rugonyi S;Marks DL;Thornburg KL;Hinds MT
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.
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DOI：
10.1002/tera.1420010204
发表时间：
1968-01-01
期刊：
TERATOLOGY
影响因子：
--
作者：
GEBHARDT, DO
通讯作者：
GEBHARDT, DO
影响因子：
3.2
作者：
Kumar, Srinivasan Dinesh;Yong, Sook-Kwin;Tay, Samuel Sam-Wah
通讯作者：
Tay, Samuel Sam-Wah
影响因子：
3.5
作者：
Liu, Aiping;Wang, Ruikang;Rugonyi, Sandra
通讯作者：
Rugonyi, Sandra
影响因子：
4.8
作者：
Chattergoon, Natasha N.;Giraud, George D.;Thornburg, Kent L.
通讯作者：
Thornburg, Kent L.
DOI：
10.1016/j.cbpc.2005.04.008
发表时间：
2005-07-01
影响因子：
2.2
作者：
Miller, RR;Burum, AL;Hart, JD
通讯作者：
Hart, JD