Short-term glucosamine infusion does not affect insulin sensitivity in humans

Overactivity of the hexosamine biosynthetic pathway may underlie hyperglyce mia-associated insulin resistance, but to date human studies are lacking. H exosamine pathway activation can be mimicked by glucosamine (GlcN). In the present placebo-controlled study we determined whether GlcN infusion affect s insulin resistance in vivo. In 18 healthy subjects, we applied the double forearm balance technique (infused arm vs. control arm) combined with the euglycemic hyperinsulinemic clamp (60 mu/m(2).min insulin) for at least 300 min. During the clamp, subjects received infusions in the brachial artery of 4 mu mol/dL.min GlcN from 90-240 min (n = 6) or from 0-300 min (n = 6) o r saline (placebo; n = 6). We studied the effects of GlcN on forearm glucos e uptake (FGU; infused arm vs. control arm, and us, placebo experiments) an d on whole body glucose uptake. GlcN infusion raised the plasma GlcN concen tration in the infusion arms to 0.42 +/- 0.14 and 0.81 +/-. 0.46 mmol/L; pl asma GlcN remained very low (<0.07 mmol/L) in the control arms and in the p lacebo group. GlcN infusion did not change forearm blood flow. During insul in, FGU increased more than 10-fold. At all time points, FGU was similar in the GlcN-infused arm compared with the control arm and was not different f rom FGU in the placebo experiments. Similar results were obtained fbr forea rm arteriovenous glucose differences or extraction and for whole body gluco se uptake. Thus, despite relevant GlcN concentrations for 5 h in the infuse d forearm, GlcN had no effect on insulin-induced glucose uptake. These resu lts do not support involvement of the hexosamine pathway in the regulation of insulin sensitivity in humans, at least not in the short-term setting.