Glucosamine-induced insulin resistance in L6 muscle cells.
BACKGROUND
Glucosamine increases flux through the hexosamine pathway, causing insulin resistance and disturbances similar to diabetic glucose toxicity.


OBJECTIVE
This study examines the effect of glucosamine on glucose uptake by cultured L6 muscle cells as a model of insulin resistance.


METHODS
Glucose uptake by L6 myotubes was measured using the non-metabolized glucose analogue 2-deoxy-d-glucose after incubation with glucosamine for 4 and 24 h, with and without insulin and several other agents (metformin, peroxovanadium and d-pinitol) that improve glucose uptake in diabetic states.


RESULTS
After 4 h, high concentrations of glucosamine (5 x 10(-3) and 10(-2) M) reduced basal and insulin-stimulated glucose uptake by up to 50%. After 24 h, the effect of insulin was completely abolished by 10(-2) M glucosamine and reduced over 50% by 5 x 10(-3) M glucosamine. Lower concentrations of glucosamine did not significantly alter glucose uptake. The effect of glucosamine could not be attributed to cytotoxicity assessed by the Trypan Blue test. Metformin, peroxovanadium and d-pinitol, each of which increased glucose uptake by L6 cells, did not prevent the decrease in glucose uptake with glucosamine.


CONCLUSIONS
Glucosamine decreased insulin-stimulated glucose uptake by L6 muscle cells, providing a potential model of insulin resistance with similarities to glucose toxicity. Insulin resistance induced by glucosamine was not reversed by three agents (metformin, peroxovanadium and d-pinitol) known to enhance or partially mimic the effects of insulin.
Bailey
C J
CJ
School of Life and Health Sciences, Aston University, Birmingham, UK. c.j.bailey@aston.ac.uk
Turner
S L
SL
D000818:Animals; D002478:Cells, Cultured; D003847:Deoxyglucose / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D005944:Glucosamine / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D032342:Muscle Cells / Q000378:metabolism*; D051381:Rats
D007328:Insulin; D003847:Deoxyglucose; D005944:Glucosamine