Effect of glucose variability on pathways associated with glucotoxicity in diabetes: Evaluation of a novel in vitro experimental approach
Language English Country Ireland Media print-electronic
Document type Comparative Study, Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't
PubMed
27103362
DOI
10.1016/j.diabres.2016.02.006
PII: S0168-8227(16)30010-9
Knihovny.cz E-resources
- Keywords
- Continuous glucose monitoring, Diabetes complications, Glycaemic variability, Hyperglycaemia, Hypoglycaemia, Pentose phosphate pathway,
- MeSH
- Apoptosis drug effects MeSH
- Biomarkers metabolism MeSH
- Diabetes Mellitus, Type 1 complications drug therapy physiopathology MeSH
- Human Umbilical Vein Endothelial Cells drug effects metabolism MeSH
- Glucose adverse effects MeSH
- Hyperglycemia etiology pathology MeSH
- Hypoglycemia etiology pathology MeSH
- Blood Glucose metabolism MeSH
- Cells, Cultured MeSH
- Real-Time Polymerase Chain Reaction MeSH
- Humans MeSH
- RNA, Messenger genetics MeSH
- Reverse Transcriptase Polymerase Chain Reaction MeSH
- Cell Proliferation drug effects MeSH
- Oligonucleotide Array Sequence Analysis MeSH
- Gene Expression Profiling MeSH
- Case-Control Studies MeSH
- In Vitro Techniques MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Evaluation Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Names of Substances
- Biomarkers MeSH
- Glucose MeSH
- Blood Glucose MeSH
- RNA, Messenger MeSH
AIMS: Glycaemic variability (GV) has been hypothesized to increase the risk of diabetes complications; however, results of clinical studies are contradictory. The effect of GV on cell phenotypes has been investigated in vitro showing that GV may have more deleterious effect on cells that high glucose itself. However, methodology used to study GV in vitro differs significantly between studies and does not reflect in vivo situation. Therefore we aimed to establish clinically relevant an in vitro experimental approach for the study of GV that reflects intra-day glucose fluctuations of subjects with type 1 diabetes mellitus (T1DM) and of healthy subjects and to test how low and high GV affect expression of genes that protects cells from hyperglycaemia-induced damage. METHODS: Human umbilical vein endothelial cells (HUVEC) were cultured 24h in medium with different glucose profiles: high GV, low GV and GV of healthy subjects-profiles created according to CGM of T1DM patients and healthy subjects. These profiles were compared to commonly used 5.5 and 25mmol/l glucose concentrations. Gene expression was determined using quantitative PCR. RESULTS: Our results showed general down-regulation of enzymes that are involved in the protection against hyperglycaemia-induced intracellular changes in both low and high GV compared to normal glycaemia similarly to the decrease induced by continuous hyperglycaemia. Gene expressions did not differ between high and low GV. CONCLUSION: Our data indicate that GV may have similar or even greater effect than continuous hyperglycaemia on the expression of several genes relevant to pathogenesis of diabetes microvascular complications.
3rd Department of Internal Medicine 1st Faculty of Medicine Charles University Prague Czech Republic
Department of Pathophysiology Faculty of Medicine Masaryk University Brno Czech Republic
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