Hyperglycemia slows embryonic growth and suppresses cell cycle via cyclin D1 and p21

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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 hyper-glycemia- 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.

Original languageEnglish (US)
Pages (from-to)234-242
Number of pages9
JournalDiabetes
Volume62
Issue number1
DOIs
StatePublished - Jan 2013

Fingerprint

Cyclin D1
Hyperglycemia
Cell Cycle
Glucose
Growth
Embryonic Structures
Facilitative Glucose Transport Proteins
Osmotic Pressure
Chick Embryo
Pregnant Women
Fetus
Cell Proliferation
Gene Expression
Pregnancy
Injections
Mortality

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Hyperglycemia slows embryonic growth and suppresses cell cycle via cyclin D1 and p21. / Scott-Drechsel, Devon E.; Rugonyi, Sandra; Marks, Daniel; Thornburg, Kent; Hinds, Monica.

In: Diabetes, Vol. 62, No. 1, 01.2013, p. 234-242.

Research output: Contribution to journalArticle

@article{28de3687e27246fdbb0dc836479a4feb,
title = "Hyperglycemia slows embryonic growth and suppresses cell cycle via cyclin D1 and p21",
abstract = "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 hyper-glycemia- 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.",
author = "Scott-Drechsel, {Devon E.} and Sandra Rugonyi and Daniel Marks and Kent Thornburg and Monica Hinds",
year = "2013",
month = "1",
doi = "10.2337/db12-0161",
language = "English (US)",
volume = "62",
pages = "234--242",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "1",

}

TY - JOUR

T1 - Hyperglycemia slows embryonic growth and suppresses cell cycle via cyclin D1 and p21

AU - Scott-Drechsel, Devon E.

AU - Rugonyi, Sandra

AU - Marks, Daniel

AU - Thornburg, Kent

AU - Hinds, Monica

PY - 2013/1

Y1 - 2013/1

N2 - 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 hyper-glycemia- 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.

AB - 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 hyper-glycemia- 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.

UR - http://www.scopus.com/inward/record.url?scp=84872033269&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84872033269&partnerID=8YFLogxK

U2 - 10.2337/db12-0161

DO - 10.2337/db12-0161

M3 - Article

VL - 62

SP - 234

EP - 242

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 1

ER -