Lipoic acid increases glucose uptake by skeletal muscles of obese-diabetic ob/ob mice

Aim: Alpha-lipoic acid has been reported to increase glucose disposal in diabetic states. This study has examined the effect of alpha-lipoic acid on glucose uptake by cultured L6 muscle cells and different types of skeletal muscles in normal lean (+/+) and severely insulin-resistant, obese-diabetic (ob/ob) mice. Methods: Glucose uptake was measured in L6 muscle cells using the non-metabolized glucose analogue 2-deoxy-D-glucose (2DG), and in isolated muscles by glucose disappearance from the incubation medium. Results: In L6 muscle cells, short-term incubations (2-12 h) with 10(-3) M alpha-lipoic acid increased glucose uptake by 40-80%, approximately the same extent as 10(-6) M insulin. Combination of the two agents produced a slightly greater increase (120% at 12 h) than either alone. Red quadriceps (mainly type 1 fibres), diaphragm (similar proportions of type 1 and 2 fibres) and abdominal muscle (mainly type 2 fibres) from normal mice incubated with 10(-3) M alpha-lipoic acid showed increased glucose uptake to a similar extent as 10(-6) M insulin in each of the three muscles. Muscles from ob/ob mice, which showed little response to insulin, showed a substantial increase (approximately 300%, p<0.05-0.01) in glucose uptake when 10(-3) M α-lipoic acid was added in the presence of insulin. The α-lipoic acid also increased glucose uptake in red quadriceps (approximately 300%, p<0.01) from ob/ob mice without added insulin. Conclusion: The results suggest that alpha-lipoic acid can increase glucose uptake by a range of normal muscle types and improve the response to insulin by insulin-resistant skeletal muscles of ob/ob mice.