Rats that are made insulin resistant by glucosamine treatment have impaired skeletal muscle insulin receptor phosphorylation

The current study sought to verify whether glucosamine (GlcN)-induced insulin resistance is associated with impaired insulin receptor (IR) autophosphorylation. Rats were given either saline or primed continuous GlcN infusion (5 μmol.kg^-1.min^-1) 10 minutes prior to and during euglycemic hyperinsulinemic clamp (primed continuous infusion of 20 mU.kg^-1.min^-1 insulin for 2 hours). IR autophosphorylation was measured in skeletal muscle after in vivo insulin stimulation (ie, during clamp) by Western blot and then retested after subsequent in vitro 0.1 to 100 nmol/L insulin stimulation (by enzyme-linked immunosorbent assay [ELISA]). Tissue PC-1 enzymatic activity was also measured. In vivo, insulin/GlcN rats had decreased (P <.01) whole body glucose uptake (37.7 ± 2.1 v 49.7 ± 2.7 mg.kg^-1.min^-1 in respect to insulin/saline), receptor autophosphorylation (37 ± 5 v 82 ± .0 arbitrary units/mg protein), and insulin receptor substrate-1 (IRS-1) phosphorylation (112% ± 15% v 198% ± 23% of saline infusion rats). Receptor autophosphorylation was correlated with whole body glucose uptake (r = 0.62, P <.05). Skeletal muscle PC-1 activity (58.8 ± 10.7 v 55.7 ± 5.8 nmol.mg^-1.min^-1) was not different in the 2 groups. Our data show that GlcN-induced insulin resistance is mediated, at least in part, by impaired skeletal muscle IR autophosphorylation.