The effect of the nitric oxide donor sodium nitroprusside on glucose uptake in human primary skeletal muscle cells.
Nitric oxide (NO) has been implicated as an important signaling molecule in the insulin-independent, contraction-mediated glucose uptake pathway and may represent a novel strategy for blood glucose control in patients with type 2 diabetes (T2DM). The current study sought to determine whether the NO donor, sodium nitroprusside (SNP) increases glucose uptake in primary human skeletal muscle cells (HSkMC) derived from both healthy individuals and patients with T2DM. Vastus lateralis muscle cell cultures were derived from seven males with T2DM (aged 54 +/-2 years, BMI 31.7 +/-1.2 kg/m(2), fasting plasma glucose 9.52+/-0.80 mmol/L) and eight healthy individuals (aged 46 +/-2 years, BMI 27.1 +/- 1.5 kg/m(2), fasting plasma glucose 4.69+/-0.12 mmol/L). Cultures were treated with both therapeutic (0.2 and 2 microM) and supratherapeutic (3, 10 and 30 mM) concentrations of SNP. An additional NO donor S-nitroso-N-acetyl-d,l-penicillamine (SNAP) was also examined at a concentration of 50 microM. Glucose uptake was significantly increased following both 30 and 60 min incubations with the supratherapeutic SNP treatments (P=0.03) but not the therapeutic SNP doses (P=0.60) or SNAP (P=0.54). There was no difference in the response between the healthy and T2DM cell lines with any treatment or dose. The current study demonstrates that glucose uptake is elevated by supratherapeutic, but not therapeutic doses of SNP in human primary skeletal muscle cells derived from both healthy volunteers and patients with T2D. These data confirm that nitric oxide donors have potential therapeutic utility to increase glucose uptake in humans, but that SNP only achieves this in supratherapeutic doses. Further study to delineate mechanisms and the therapeutic window is warranted.
Henstridge
Darren C
DC
Alfred & Baker Medical Unit, Baker IDI Heart and Diabetes Institute, Melbourne 8008, Vic., Australia.
Drew
Brian G
BG
Formosa
Melissa F
MF
Natoli
Alaina K
AK
Cameron-Smith
David
D
Duffy
Stephen J
SJ
Kingwell
Bronwyn A
BA
D000328:Adult; D000704:Analysis of Variance; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*; D052097:Quadriceps Muscle / Q000166:cytology
D007328:Insulin; D020030:Nitric Oxide Donors; D009599:Nitroprusside; D009569:Nitric Oxide; D005947:Glucose