Induction of insulin resistance by glucosamine reduces blood flow but not interstitial levels of either glucose or insulin

To study the effects of a glucosamine infusion on skeletal muscle metabolis m, microdialysis was performed in the medial femoral muscle in Sprague-Dawl ey rats during a euglycemic-hyperinsulinemic clamp (insulin infusion 18 mU . kg(-1) . min(-1)). During steady-state clamping conditions (70 min), an i nfusion of glucosamine (30 mu mol . kg(-1) . min(-1)) or saline was given f or 240 min, Blood flow was measured by the microsphere technique at the end of the clamp, An similar to 36% (P < 0.001) reduction in the glucose infus ion rate was seen after 170 min in the glucosamine-treated rats compared wi th control rats, There were no significant differences in interstitial or p lasma levels of either insulin or glucose between the two groups, Both inte rstitial (2.31 +/- 0.18 vs. 1.71 +/- 0.24 mmol/l, P < 0.05) and arterial pl asma lactate concentrations (1.29 +/- 0.09 vs. 0.79 +/- 0.09 mmol/l, P < 0. 01) were significantly higher in control rats compared with glucosamine-tre ated rats, Blood flow was significantly reduced in hind limb femoral muscle s in the glucosamine-treated rats compared with control rats, The roost pro nounced reduction in blood flow was seen in the Soleus muscle (27.6 +/- 3.4 vs. 14.7 +/- 2.0 ml . 100 g(-1) . min(-1), P < 0.01). These results demons trate that induction of insulin resistance bf glucosamine results in a redu ction of the blood flow rate as well as the uptake of glucose and tho produ ction of lactate in skeletal muscle, As a result of the inhibited glucose m etabolism, the interstitial glucose concentration was unchanged despite the reduced blood flow after glucosamine administration, The data suggest the importance of regulation of blood flow bg nonoxidative metabolism of glucos e in resting muscle.