TY - JOUR
T1 - Metabolic interactions of AGE inhibitor pyridoxamine and antioxidant α-lipoic acid following 22 weeks of treatment in obese Zucker rats
AU - Muellenbach, Elizabeth M.
AU - Diehl, Cody J.
AU - Teachey, Mary K.
AU - Lindborg, Katherine A.
AU - Hasselwander, Oliver
AU - Matuschek, Markus
AU - Henriksen, Erik J.
N1 - Funding Information:
The present study was supported by a grant from BASF AG, Ludwigshafen, Germany.
PY - 2009/4/10
Y1 - 2009/4/10
N2 - 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.
AB - 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.
KW - Insulin resistance
KW - Oxidative stress
KW - Skeletal muscle
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U2 - 10.1016/j.lfs.2009.01.021
DO - 10.1016/j.lfs.2009.01.021
M3 - Article
C2 - 19302804
AN - SCOPUS:62749098225
SN - 0024-3205
VL - 84
SP - 563
EP - 568
JO - Life Sciences
JF - Life Sciences
IS - 15-16
ER -