This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pouwels, M.-J. J. Articles by Tack, C. J. Search for Related Content PubMed PubMed Citation Articles by Pouwels, M.-J. J. Articles by Tack, C. J.

Short-Term Glucosamine Infusion Does Not Affect Insulin Sensitivity in Humans¹

Divisions of General Internal Medicine (M.-J.P., J.R.J., J.A.L., P.S., C.J.T.) and Endocrinology (M.-J.M.P.), Department of Medicine, and Department of Chemical Endocrinology (P.N.S.), University Medical Center, 6500 HB Nijmegen, The Netherlands

Address all correspondence and requests for reprints to: Marie-Jose Pouwels, M.D., Division of Endocrinology, University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. E-mail: m.pouwels{at}endo.azn.nl

Overactivity of the hexosamine biosynthetic pathway may underlie hyperglycemia-associated insulin resistance, but to date human studies are lacking. Hexosamine pathway activation can be mimicked by glucosamine (GlcN). In the present placebo-controlled study we determined whether GlcN infusion affects 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/m²·min insulin) for at least 300 min. During the clamp, subjects received infusions in the brachial artery of 4 µmol/dL·min GlcN from 90–240 min (n = 6) or from 0–300 min (n = 6) or saline (placebo; n = 6). We studied the effects of GlcN on forearm glucose uptake (FGU; infused arm vs. control arm, and vs. placebo experiments) and on whole body glucose uptake.

GlcN infusion raised the plasma GlcN concentration in the infusion arms to 0.42 ± 0.14 and 0.81 ± 0.46 mmol/L; plasma GlcN remained very low (<0.07 mmol/L) in the control arms and in the placebo group. GlcN infusion did not change forearm blood flow. During insulin, 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 from FGU in the placebo experiments. Similar results were obtained for forearm arteriovenous glucose differences or extraction and for whole body glucose uptake. Thus, despite relevant GlcN concentrations for 5 h in the infused forearm, GlcN had no effect on insulin-induced glucose uptake. These results do not support involvement of the hexosamine pathway in the regulation of insulin sensitivity in humans, at least not in the short-term setting.

This article has been cited by other articles:

				B A Biggee, C M Blinn, M Nuite, J E Silbert, and T E McAlindon Effects of oral glucosamine sulphate on serum glucose and insulin during an oral glucose tolerance test of subjects with osteoarthritis Ann Rheum Dis, February 1, 2007; 66(2): 260 - 262. [Abstract] [Full Text] [PDF]

				R. Muniyappa, R. J. Karne, G. Hall, S. K. Crandon, J. A. Bronstein, M. R. Ver, G. L. Hortin, and M. J. Quon Oral Glucosamine for 6 Weeks at Standard Doses Does Not Cause or Worsen Insulin Resistance or Endothelial Dysfunction in Lean or Obese Subjects Diabetes, November 1, 2006; 55(11): 3142 - 3150. [Abstract] [Full Text] [PDF]

				J. L Stumpf and S.-W. Lin Effect of Glucosamine on Glucose Control Ann. Pharmacother., April 1, 2006; 40(4): 694 - 698. [Abstract] [Full Text] [PDF]

				M. G. Buse Hexosamines, insulin resistance, and the complications of diabetes: current status Am J Physiol Endocrinol Metab, January 1, 2006; 290(1): E1 - E8. [Abstract] [Full Text] [PDF]

				D. A. Scroggie, A. Albright, and M. D. Harris The Effect of Glucosamine-Chondroitin Supplementation on Glycosylated Hemoglobin Levels in Patients With Type 2 Diabetes Mellitus: A Placebo-Controlled, Double-blinded, Randomized Clinical Trial Arch Intern Med, July 14, 2003; 163(13): 1587 - 1590. [Abstract] [Full Text] [PDF]

				J. G. Yu, S. M. Boies, and J. M. Olefsky The Effect of Oral Glucosamine Sulfate on Insulin Sensitivity in Human Subjects Diabetes Care, June 1, 2003; 26(6): 1941 - 1942. [Full Text] [PDF]

				M.-J. J. Pouwels, P. N. Span, C. J. Tack, A. J. Olthaar, C. G. J. Sweep, B. G. van Engelen, J. G. de Jong, J. A. Lutterman, and A. R. Hermus Muscle Uridine Diphosphate-Hexosamines Do Not Decrease Despite Correction of Hyperglycemia-Induced Insulin Resistance in Type 2 Diabetes J. Clin. Endocrinol. Metab., November 1, 2002; 87(11): 5179 - 5184. [Abstract] [Full Text] [PDF]

				K. Pavelka, J. Gatterova, M. Olejarova, S. Machacek, G. Giacovelli, and L. C. Rovati Glucosamine Sulfate Use and Delay of Progression of Knee Osteoarthritis: A 3-Year, Randomized, Placebo-Controlled, Double-blind Study Arch Intern Med, October 14, 2002; 162(18): 2113 - 2123. [Abstract] [Full Text] [PDF]