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Insulinotropic compounds decrease endothelial cell survival.
Irina I Zaitseva1, Per-Olof Berggren1, Sergei V Zaitsev2
1Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, SE-17176 Stockholm, Sweden.
Summary
Insulinotropic compounds and vascular endothelial growth factor (VEGF) interact with high glucose, affecting blood vessel cell survival. This interplay is crucial for developing new diabetes medications.
Area of Science:
- Endocrinology
- Vascular Biology
- Pharmacology
Background:
- Hyperglycemia damages vascular endothelial cells, contributing to diabetic complications.
- Vascular endothelial growth factor (VEGF) plays a role in endothelial cell survival.
Purpose of the Study:
- Investigate the effects of insulinotropic compounds and elevated glucose on endothelial cells.
- Examine these effects in the presence and absence of VEGF.
Main Methods:
- Human umbilical vein endothelial cells (HUVECs) were treated with glibenclamide, repaglinide, and insulinotropic imidazolines under high glucose conditions.
- Assessed HUVEC viability, proliferation, and nitric oxide (NO) production with or without VEGF.
Main Results:
- Hyperglycemia reduced VEGF's pro-survival effects on HUVECs.
- Glibenclamide and repaglinide decreased HUVEC viability at high glucose without VEGF, but not with VEGF.
- Repaglinide enhanced NO production in the presence of VEGF.
- Efaroxan reduced viability with VEGF and high glucose, while RX871024 decreased survival regardless of VEGF.
Conclusions:
- An interplay exists between insulinotropic compounds, VEGF, and glucose levels impacting endothelial cell survival.
- This interaction must be considered when designing novel oral antidiabetic drugs.
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