Differential effects of lipoic acid stereoisomers on glucose metabolism in insulin-resistant skeletal muscle
| Autor: | Stephan Jacob, Hans J. Tritschler, Donovan L. Fogt, Jason Y. Hokama, Ryan S. Streeper, Erik J. Henriksen |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Blood Glucose
medicine.medical_specialty Physiology Endocrinology Diabetes and Metabolism medicine.medical_treatment Biology Carbohydrate metabolism Deoxyglucose Fatty Acids Nonesterified Antioxidants chemistry.chemical_compound Insulin resistance Reference Values Physiology (medical) Internal medicine medicine Hyperinsulinemia Animals Humans Insulin Obesity Glycogen synthase Muscle Skeletal Thioctic Acid Glucose transporter Biological Transport Stereoisomerism Metabolism medicine.disease Rats Rats Zucker Lipoic acid Endocrinology Glucose chemistry biology.protein Female Insulin Resistance Glycogen |
| Zdroj: | The American journal of physiology. 273(1 Pt 1) |
| ISSN: | 0002-9513 |
| Popis: | The racemic mixture of the antioxidant alpha-lipoic acid (ALA) enhances insulin-stimulated glucose metabolism in insulin-resistant humans and animals. We determined the individual effects of the pure R-(+) and S-(-) enantiomers of ALA on glucose metabolism in skeletal muscle of an animal model of insulin resistance, hyperinsulinemia, and dyslipidemia: the obese Zucker (fa/fa) rat. Obese rats were treated intraperitoneally acutely (100 mg/kg body wt for 1 h) or chronically [10 days with 30 mg/kg of R-(+)-ALA or 50 mg/kg of S-(-)-ALA]. Glucose transport [2-deoxyglucose (2-DG) uptake], glycogen synthesis, and glucose oxidation were determined in the epitrochlearis muscles in the absence or presence of insulin (13.3 nM). Acutely, R-(+)-ALA increased insulin-mediated 2-DG-uptake by 64% (P < 0.05), whereas S-(-)-ALA had no significant effect. Although chronic R-(+)-ALA treatment significantly reduced plasma insulin (17%) and free fatty acids (FFA; 35%) relative to vehicle-treated obese animals, S-(-)-ALA treatment further increased insulin (15%) and had no effect on FFA. Insulin-stimulated 2-DG uptake was increased by 65% by chronic R-(+)-ALA treatment, whereas S-(-)-ALA administration resulted in only a 29% improvement. Chronic R-(+)-ALA treatment elicited a 26% increase in insulin-stimulated glycogen synthesis and a 33% enhancement of insulin-stimulated glucose oxidation. No significant increase in these parameters was observed after S-(-)-ALA treatment. Glucose transporter (GLUT-4) protein was unchanged after chronic R-(+)-ALA treatment but was reduced to 81 +/- 6% of obese control with S-(-)-ALA treatment. Therefore, chronic parenteral treatment with the antioxidant ALA enhances insulin-stimulated glucose transport and non-oxidative and oxidative glucose metabolism in insulin-resistant rat skeletal muscle, with the R-(+) enantiomer being much more effective than the S-(-) enantiomer. |
| Databáze: | OpenAIRE |
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