Insulin Resistance Induced by Glucosamine in Fructose-fed Rats

Abstract

Glucosamine has been widely used to treat osteoporosis in clinic and it shows an effect on hexosamine biosynthetic pathway in glucose-induced insulin resistance. However, glucosamine and chronic hyperglycemia is not correlative. Thus, we used C₂C₁₂ cell line to carry out the uptake assay of 2-[¹⁴C]-deoxy-d-glucose and [³H]-glucosamine. Glucosamine inhibited the in vitro glucose uptake in a concentration-dependent manner. The glucose transporter GLUT4 prepared for [³H]-glucosamine uptake showed a concentration-dependent competition between glucose and glucosamine uptake. The effects of glucosamine on glucose tolerance and homeostasis model assessment (HOMA) were also determined in normal Wistar and fructose-fed rats. Both plasma glucose levels and/or HOMA index were not changed in normal rats treated with glucosamine as compared with the saline-treated control. However, we found that glucosamine exhibited an effect on the expression of farnesoid X receptor in liver to exacerbate the values of HOMA and accelerate the development of insulin resistance in fructose-fed rats. Thus, glucosamine should be applied with caution in type-2 diabetic patients.

Key words

FXR - glucosamine - glucose transporter GLUT4 - insulin resistance - glucose tolerance test

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