부산대학교 도서관

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−1insulin 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 v49.7 ± 2.7 mg · kg−1· min−1in respect to insulin/saline), receptor autophosphorylation (37 ± 5 v82 ± .0 arbitrary units/mg protein), and insulin receptor substrate-1 (IRS-1) phosphorylation (112% ± 15% v198% ± 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 v55.7 ± 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.