title: Chemical and functional changes of human insulin by in vitro incubation with blood from diabetic patients in oxidative stress.
abstract: Oxidative stress damage to biomolecules has been implicated in several diseases including diabetes mellitus. In the present study, we investigated the effect of oxidative stress in whole blood (WB) from diabetic patients (n = 60) on recombinant human insulin. Insulin was incubated with WB obtained from diabetic patients (DP) who had hyperglycemia (>300 mg/dL) or from 41 healthy volunteers (HV). Whole blood of DP, unlike WB of HV, induced higher values of formazan (142%), dityrosines (279%), and carbonyls (58%) in the insulin residues. Interestingly, the insulin modified by WB of DP showed less hypoglycemic activity in rat (30%) in comparison with insulin incubated with WB of HV. The incubation of insulin in WB from DP induces chemical changes in insulin and a decrease in its biological activity, events that might be associated with the high levels of oxidative stress markers found in the plasma of these patients.
authors.affiliation: General Hospital, Nacional Medical Center La Raza, Mexican Institute for Social Security, Mexico City, Mexico.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Montes-Cortes
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Hicks
authors.forename: Guillermo M
authors.initials: GM
authors.lastname: Ceballos-Reyes
authors.forename: Jose R
authors.initials: JR
authors.lastname: Garcia-Sanchez
authors.forename: Rafael
authors.initials: R
authors.lastname: Medina-Navarro
authors.forename: Ivonne M
authors.initials: IM
authors.lastname: Olivares-Corichi
mesh_terms: D019540:Area Under Curve; D015415:Biomarkers; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D005562:Formazans / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007274:Injections, Intraperitoneal; D007328:Insulin / Q000737:chemistry / Q000378:metabolism*; D007501:Iron / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D050050:Protein Carbonylation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D005562:Formazans; D007004:Hypoglycemic Agents; D007328:Insulin; D017382:Reactive Oxygen Species; D014443:Tyrosine; D008315:Malondialdehyde; C007543:dityrosine; D007501:Iron