title: Vascular effects of metabolic inhibition by 2-deoxy-D-glucose in humans.
abstract: 2-Deoxy-D-glucose (2DG) is a structural analogue of glucose that inhibits the glycolytic pathway. In vitro 2DG induced vasodilation, which was inhibited by glibenclamide (blocker of ATP-dependent potassium channels). The vasodilation induced by 2DG may be an interesting model for metabolic vasodilation. In this study, we investigated whether 2DG induces vasodilation in the human skeletal muscle vascular bed and whether this vasodilation was inhibited by glibenclamide. We measured forearm blood flow (FBF, venous occlusion plethysmography) in response to intra-arterial 2DG (0.4 and 0.8 mg/min x dl of forearm volume, each dose for 30 min), either alone or with co-infusion of insulin to increase the cellular 2DG uptake, and compared the results with insulin infusion alone. Glibenclamide infusion (1.0 microg/min x dl) was added in a subgroup. 2DG alone did not change FBF ratio (experimental/control arm, 11 +/- 9%, p = 0.34), but 2DG with insulin significantly increased FBF ratio (32 +/- 17%, p = 0.04). The increase in FBF by 2DG and insulin was significantly more pronounced than the vasodilation induced by insulin alone (p = 0.03). Co-infusion of glibenclamide had no effect on the vasodilation induced by 2DG and insulin (percentage increase in FBF ratio 11 +/- 18% without and 17 +/- 12% with glibenclamide, p = 0.85). In conclusion, 2DG induces manifest vasodilation in humans when infused in combination with insulin. This vasodilation is not mediated by ATP-dependent potassium channels.
authors.affiliation: Department of General Internal Medicine, University Medical Center St. Radboud, Nijmegen, The Netherlands.
authors.forename: E J
authors.initials: EJ
authors.lastname: Abbink
authors.forename: C J
authors.initials: CJ
authors.lastname: Tack
authors.forename: P
authors.initials: P
authors.lastname: Smits
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D000963:Antimetabolites / Q000494:pharmacology*; D003847:Deoxyglucose / Q000494:pharmacology*; D004338:Drug Combinations; D005260:Female; D005542:Forearm / Q000098:blood supply; D005905:Glyburide / Q000494:pharmacology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
chemical_list: D000963:Antimetabolites; D004338:Drug Combinations; D007004:Hypoglycemic Agents; D007328:Insulin; D003847:Deoxyglucose; D005905:Glyburide