Related Experiment Video
Updated: May 16, 2026

A High-content In Vitro Pancreatic Islet β-cell Replication Discovery Platform
Published on: July 16, 2016
Hyperglycemia slows embryonic growth and suppresses cell cycle via cyclin D1 and p21
Devon E Scott-Drechsel1, Sandra Rugonyi, Daniel L Marks
1Biomedical Engineering Department, Oregon Health & Science University, Portland, Oregon, USA.
Insights
High blood sugar during pregnancy significantly increases the risk of fetal heart defects. This study shows hyperglycemia in chick embryos slows cell growth, potentially causing these developmental issues.
Area of Science:
- Developmental biology
- Endocrinology
- Cardiovascular science
Background:
- Diabetes in pregnancy elevates fetal risk for cardiac malformations due to hyperglycemia and osmotic stress.
- Understanding the mechanisms linking maternal hyperglycemia to embryonic heart development is crucial.
Purpose of the Study:
- To investigate the impact of pulsed and sustained hyperglycemia on early heart development in chick embryos.
- To identify cellular and molecular changes associated with hyperglycemia-induced developmental delays.
Main Methods:
- Two models of hyperglycemia were used: pulsed (daily glucose) and sustained (single yolk injection).
- Embryo size, mortality, and development were assessed.
- Gene expression of glucose transporter GLUT1 and cell cycle regulators (p21, cyclin D1) were analyzed.
- Cell proliferation in the heart outflow tract was quantified.
Main Results:
- Both hyperglycemia models reduced embryo size, increased mortality, and delayed development.
- Sustained hyperglycemia decreased GLUT1 expression and led to hyperosmolarity.
- Reduced proliferation of myocardial and endocardial cells was observed in the sustained model.
- Sustained hyperglycemia increased the cell cycle inhibitor p21 and decreased the promoter cyclin D1.
Conclusions:
- Hyperglycemia-induced developmental delays are linked to slowed cell cycle progression and reduced cellular proliferation.
- These cellular changes may underlie the cardiac defects observed in fetuses of diabetic mothers.
- The study provides insights into the mechanisms of diabetic embryopathy affecting heart development.
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 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.
Related Concept Videos
Cell Specific Gene Expression
Hypoglycemia and Glucagon
Inhibition of Cdk Activity
Diabetes Mellitus: Type 2 and Gestational
Pathophysiology of Diabetes
Type 1 diabetes is characterized by autoimmune-mediated destruction of pancreatic β cells, with environmental factors potentially triggering this process in genetically susceptible individuals. Despite many not having a family history, certain genes increase susceptibility, suggesting a...
Hormones Regulating Blood Glucose
In addition to accelerating glucose uptake and utilization, insulin has...

