C J Bailey1, S L Turner. 1. School of Life and Health Sciences, Aston University, Birmingham, UK. c.j.bailey@aston.ac.uk
Abstract
BACKGROUND: Glucosamine increases flux through the hexosamine pathway, causing insulin resistance and disturbances similar to diabetic glucose toxicity. AIM: 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. CONCLUSION: 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.
BACKGROUND:Glucosamine increases flux through the hexosamine pathway, causing insulin resistance and disturbances similar to diabetic glucose toxicity. AIM: 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. CONCLUSION: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.
Authors: G A Raciti; C Iadicicco; L Ulianich; B F Vind; M Gaster; F Andreozzi; M Longo; R Teperino; P Ungaro; B Di Jeso; P Formisano; F Beguinot; C Miele Journal: Diabetologia Date: 2010-02-18 Impact factor: 10.122
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