Abstract | AIMS/HYPOTHESIS:
Insulin exerts a direct action on vascular cells, thereby affecting the outcome and progression of diabetic vascular complications. However, the mechanism through which insulin signalling is impaired in the endothelium of diabetic individuals remains unclear. In this work, we have evaluated the role of the AGE precursor methylglyoxal (MGO) in generating endothelial insulin resistance both in cells and in animal models. METHODS: Time course experiments were performed on mouse aortic endothelial cells (MAECs) incubated with 500 μmol/l MGO. The glyoxalase-1 inhibitor S-p-bromobenzylglutathione-cyclopentyl-diester (SpBrBzGSHCp2) was used to increase the endogenous levels of MGO. For the in vivo study, an MGO solution was administrated i.p. to C57BL/6 mice for 7 weeks. RESULTS: CONCLUSIONS/INTERPRETATION: MGO impairs the action of insulin on the endothelium both in vitro and in vivo, at least in part through an ERK1/2-mediated mechanism. These findings may be instrumental in developing novel strategies for preserving endothelial function in diabetes.
|
Authors | Cecilia Nigro, Gregory A Raciti, Alessia Leone, Thomas H Fleming, Michele Longo, Immacolata Prevenzano, Francesca Fiory, Paola Mirra, Vittoria D'Esposito, Luca Ulianich, Peter P Nawroth, Pietro Formisano, Francesco Beguinot, Claudia Miele |
Journal | Diabetologia
(Diabetologia)
Vol. 57
Issue 7
Pg. 1485-94
(Jul 2014)
ISSN: 1432-0428 [Electronic] Germany |
PMID | 24759959
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Insulin
- Insulin Receptor Substrate Proteins
- Irs1 protein, mouse
- S-4-bromobenzylglutathione cyclopentyl diester
- Nitric Oxide
- Pyruvaldehyde
- Nitric Oxide Synthase Type III
- Proto-Oncogene Proteins c-akt
- Glutathione
|
Topics |
- Animals
- Endothelial Cells
(drug effects, metabolism)
- Glutathione
(analogs & derivatives, pharmacology)
- Insulin
(metabolism)
- Insulin Receptor Substrate Proteins
(metabolism)
- Insulin Resistance
(physiology)
- Mice
- Nitric Oxide
(biosynthesis)
- Nitric Oxide Synthase Type III
(metabolism)
- Phosphorylation
- Proto-Oncogene Proteins c-akt
(metabolism)
- Pyruvaldehyde
(pharmacology)
- Signal Transduction
(drug effects)
|