Insulin resistance induced by glucosamine in fructose-fed rats.

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 C (2)C (12) 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.