Metabolic interactions of AGE inhibitor pyridoxamine and antioxidant α-lipoic acid following 22 weeks of treatment in obese Zucker rats

Elizabeth M. Muellenbach, Cody J. Diehl, Mary K. Teachey, Katherine A. Lindborg, Oliver Hasselwander, Markus Matuschek, Erik J. Henriksen

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Aims: The advanced glycation end product inhibitor pyridoxamine (PYR) and the antioxidant α-lipoic acid (LA) interact to ameliorate insulin resistance in obese Zucker rats following short-term (6-week) treatment. This study was designed to ascertain whether these unique interactive effects of PYR and LA remain manifest following longer-term (22-week) treatment. Main methods: Female obese Zucker rats received vehicle (OV), PYR (OP, 60 mg/kg body wt), racemic LA (rac-LA; OM, 92 mg/kg), the R-(+)-enantiomer of LA (R-LA; OR, 92 mg/kg), or combined treatments with PYR and rac-LA (OPM) or PYR and R-LA (OPR), daily for 22 weeks. Key findings: Individual and combined treatments with PYR, rac-LA, and R-LA significantly (p < 0.05) inhibited skeletal muscle protein carbonyls (28-36%), a marker of oxidative damage, and triglyceride levels (21-51%). Plasma free fatty acids were reduced in OM (9%), OR (11%), and OPM (16%), with the greatest decrease (26%) elicited in OPR. HOMA-IR, an index of fasting insulin resistance, was decreased in OP (14%) and OPM (17%) groups, with the greatest inhibition (22%) in OPR. Insulin resistance (glucose-insulin index) was lowered (20%) only in OPR. Insulin-mediated glucose transport in isolated skeletal muscle was improved in OM (34%), OR (33%), OPM (48%) and OPR (31%) groups. Significance: Important interactions between PYR and LA for improvements in glucose and lipid metabolism in the female obese Zucker rat are manifest following a 22-week treatment regimen, providing further evidence for targeting oxidative stress as a strategy for reducing insulin resistance.

Original languageEnglish (US)
Pages (from-to)563-568
Number of pages6
JournalLife Sciences
Volume84
Issue number15-16
DOIs
StatePublished - Apr 10 2009

Keywords

  • Insulin resistance
  • Oxidative stress
  • Skeletal muscle

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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