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 micromol x kg(-1) x min(-1)) 10 minutes prior to and during euglycemic hyperinsulinemic clamp (primed continuous infusion of 20 mU x kg(-1) x 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 x kg(-1) x 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 x mg(-1) x 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.
D000818:Animals; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D005944:Glucosamine / Q000008:administration & dosage*; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000097:blood; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance; D008297:Male; D018482:Muscle, Skeletal / Q000737:chemistry* / Q000201:enzymology; D010750:Phosphoproteins / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D010766:Phosphorylation; D011755:Pyrophosphatases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011972:Receptor, Insulin / Q000378:metabolism*
D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D010750:Phosphoproteins; D011972:Receptor, Insulin; D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases; D005947:Glucose; D005944:Glucosamine