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Structural and functional changes in the insulin molecule produced by oxidative stress.
Rafael Medina-Navarro1, Alberto M Guzmán-Grenfell, Ivonne Olivares-Corichi
1Laboratorio de Metabolismo Experimental, Centro de Investigación Biomédica de Michoacán, (CIBIMI-IMSS), Michoacán, México. rafael.medina@imss.gob.mx
Methods in Molecular Biology (Clifton, N.J.)
|January 15, 2010
Summary
Oxidative stress damages insulin, diminishing its blood sugar-lowering effect. Hydroxyl radical and acrolein modifications impair insulin function, highlighting potential structural and functional damage.
Area of Science:
- Biochemistry
- Physiology
- Molecular Biology
Background:
- Oxidative stress causes protein modifications like cross-links and aggregation, affecting protein function.
- Insulin is susceptible to conformational changes and aggregation, which can impair its biological activity.
Purpose of the Study:
- To investigate the effects of hydroxyl radical and acrolein modification on insulin's biological activity.
- To understand the structural and functional consequences of oxidative stress on insulin.
Main Methods:
- In vivo studies in rats and in vitro studies using adipocytes were conducted.
- Insulin was modified by hydroxyl radical and exposed to acrolein.
- Hypoglycemic effects and carbonyl formation were assessed.
Main Results:
- Both hydroxyl radical and acrolein diminished insulin's hypoglycemic effect in vivo.
- Acrolein-induced damage involved carbonylation, not intermolecular cross-links or aggregates, and was enhanced at alkaline pH.
- Hydroxyl radical caused tyrosine derivative formation and non-aldehyde-dependent carbonyls in insulin.
Conclusions:
- Oxidative stress significantly damages insulin structure and function, impairing its hypoglycemic activity.
- Acrolein and hydroxyl radical induce distinct modifications, with acrolein's effect linked to carbonylation and aldolic condensation.
- These findings serve as a prototype for understanding oxidative stress-induced damage to insulin.
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