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Insulinotropic compounds decrease endothelial cell survival
- Source :
- Toxicology in Vitro. 33:1-8
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- Objectives Hyperglycemia induces damage of vascular endothelial cells leading to diabetic complications. We investigated the effects of insulinotropic compounds and elevated glucose on endothelial cells in the absence or presence of vascular endothelial growth factor (VEGF). Results Human umbilical vein endothelial cells (HUVECs) were treated with glibenclamide, repaglinide and insulinotropic imidazolines at high glucose concentration in the presence or absence of VEGF and viability, proliferation and nitric oxide production were measured. Hyperglycemia inhibited pro-survival effects of VEGF on endothelial cells. Glibenclamide and repaglinide decreased HUVEC viability at elevated glucose concentration in the absence but not in the presence of VEGF, without affecting HUVEC proliferation. Repaglinide also had some positive influence on HUVEC function elevating NO production in the presence of VEGF. Imidazolines showed different activities on endothelial cell survival. Efaroxan diminished HUVEC viability at elevated glucose concentration in the presence, however not in the absence of VEGF, while RX871024 decreased HUVEC survival regardless of the presence of VEGF. Significance of the study Our data demonstrate an important interplay between the actual insulinotropic compounds, VEGF and ambient glucose concentration affecting the survival of the vascular endothelial cells. Consequently, this interplay needs to be taken into consideration when designing novel oral antidiabetic compounds.
- Subjects :
- Vascular Endothelial Growth Factor A
0301 basic medicine
medicine.medical_specialty
Indoles
Cell Survival
Imidazoline receptor
Nitric Oxide
Toxicology
Umbilical vein
Nitric oxide
Glibenclamide
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Piperidines
Internal medicine
Glyburide
Human Umbilical Vein Endothelial Cells
medicine
Humans
Hypoglycemic Agents
Dimethyl Sulfoxide
Endothelial dysfunction
Cells, Cultured
Benzofurans
Cell Proliferation
business.industry
Imidazoles
General Medicine
medicine.disease
Repaglinide
Endothelial stem cell
Vascular endothelial growth factor
Glucose
030104 developmental biology
Endocrinology
chemistry
Carbamates
business
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- ISSN :
- 08872333
- Volume :
- 33
- Database :
- OpenAIRE
- Journal :
- Toxicology in Vitro
- Accession number :
- edsair.doi.dedup.....d95231e0002fb86abe1e665867fc3f8e