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


CONCLUSIONS
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.
Eason
R C
RC
School of Pharmacy, Aston University, Birmingham, UK.
Archer
H E
HE
Akhtar
S
S
Bailey
C J
CJ
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival; D003847:Deoxyglucose / Q000493:pharmacokinetics; D005947:Glucose / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D008820:Mice, Obese; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D009928:Organ Specificity; D008063:Thioctic Acid / Q000494:pharmacology*
D008063:Thioctic Acid; D003847:Deoxyglucose; D005947:Glucose