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 alpha-lipoic acid was added in the presence of insulin. The alpha-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.

The therapeutic use of lipoic acid in diabetes: a current perspective.

Lipoic acid and its reduced derivative, dihydrolipoic acid (DHLA) are highly promising antioxidant agents, which are potent attenuators of reactive species-mediated damage in vitro and in animal studies. Lipoic acid is a universal antioxidant, effective in lipophilic and aqueous environments. In contrast to an equivalent endogenous agent, such as oxidised glutathione (GSSG), lipoic acid acts as an antioxidant in its oxidised form. Lipoic acid has been evaluated in diabetic polyneuropathy, a condition which is thought to result in part from oxidant damage caused by long-term hyperglycaemia. Diabetic patients are prone to incur enhanced cellular free radical formation and reduced antioxidant defence. Treatment with lipoic acid has improved nerve conduction velocity during studies in diabetic animals. Trials in diabetic patients have often observed some relief of neuropathic symptoms during treatment with lipoic acid, but consistent objective benefits have been difficult to establish. Lipoic acid is now used in Germany for the treatment of diabetic neuropathy and definitive evidence of efficacy should arise from postmarketing surveillance studies. It is possible that lipoic acid may be more effective as a long-term dietary supplement aimed at the prophylactic protection of diabetics from complications.