Effects of the nitric oxide donor, sodium nitroprusside, on resting leg glucose uptake in patients with type 2 diabetes.
OBJECTIVE
Nitric oxide (NO) has been implicated as an important signalling molecule in the contraction-mediated glucose uptake pathway and may represent a novel strategy for blood glucose control. The current study sought to determine whether acute infusion of the NO donor, sodium nitroprusside (SNP), increases leg glucose uptake at rest in patients with type 2 diabetes.


METHODS
Fifteen male patients with type 2 diabetes (aged 54+/-4 years, mean+/-SD) were entered into a randomised, cross-over design study, examining the effect of a 30-min intra-femoral infusion of SNP on leg glucose uptake. Comparison was made with a 30-min infusion of verapamil, titrated to elicit similar leg blood flow responses to SNP. Leg blood flow was measured by thermodilution in the femoral vein, and leg glucose uptake was calculated as the product of leg blood flow and the femoral arterio-venous (A-V) glucose concentration gradient.


RESULTS
The two drugs increased leg blood flow to a similar extent (p=0.50). Both leg A-V glucose concentration gradient (SNP 0.12+/-0.05, verapamil -0.06+/-0.04 mmol/l; mean+/- SEM, p=0.03) and leg glucose uptake (SNP 0.17+/-0.09, verapamil -0.09+/-0.06 mmol/min; p=0.03) were higher with the SNP treatment than with verapamil. These results occurred independently of any significant difference in plasma insulin concentration between drugs (p=0.56).


CONCLUSIONS
Acute infusion of SNP resulted in greater glucose uptake relative to verapamil. NO may therefore be an important mediator of peripheral glucose disposal and a potential therapeutic target in patients with type 2 diabetes.
Henstridge
D C
DC
Alfred & Baker Medical Unit, Baker Heart Research Institute, St Kilda Rd Central, P.O. Box 6492, 8008, Melbourne, VIC, Australia.
Kingwell
B A
BA
Formosa
M F
MF
Drew
B G
BG
McConell
G K
GK
Duffy
S J
SJ
D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D006801:Humans; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood; D007866:Leg / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000502:physiology; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000494:pharmacology*; D009599:Nitroprusside / Q000008:administration & dosage / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D012146:Rest; D013997:Time Factors; D014700:Verapamil / Q000008:administration & dosage / Q000494:pharmacology
D001786:Blood Glucose; D002121:Calcium Channel Blockers; D007328:Insulin; D020030:Nitric Oxide Donors; D009599:Nitroprusside; D009569:Nitric Oxide; D014700:Verapamil