Acute effects of exogenous nitric oxide on glucose uptake in skeletal muscle of normoglycaemic and diabetic rats.
BACKGROUND
The role of nitric oxide (NO) in the modulation of basal and insulin-stimulated glucose uptake remains controversial. The aim of this study was to investigate the role of NO released from its donors, S-nitrosoglutathione (GSNO) and S-nitroso-N-acetylpenicillamine (SNAP), on glucose uptake in skeletal muscle of normoglyceamic and type 2 diabetic rats.


METHODS
Skeletal muscle strips of type 2 diabetic and normoglycaemic Sprague-Dawley rats were incubated with or without various concentrations (200 microM, 500 microM, 1000 microM, 10 mM & 20 mM) of SNAP or GSNO in the presence or absence of insulin (100 nM or 10 microM). The associated radioactivity was determined by liquid scintillation counting in a Beckman LS6000 scintillation counter programmed for dual-channel counting.


RESULTS
SNAP and GSNO at 1000 microM significantly elevated basal and insulin-stimulated 2-deoxyglucose uptake (P<0.05) in normoglycaemic and diabetic rats. Millimolar concentrations (10 & 20 mM) of GSNO and SNAP significantly decreased basal and insulin-stimulated glucose uptake in skeletal muscle strips of normoglycaemic and type 2 diabetic rats in a concentration-dependent manner (P<0.05). The inhibition of insulin-stimulated glucose uptake was greater in the diabetic rats using both NO donors compared with normoglycaemic rats (P<0.05).


CONCLUSIONS
The stimulatory effect of micromolar concentrations of GSNO and SNAP enhances basal and insulin-stimulated glucose uptake in normoglycaemic and type 2 diabetic rats, however higher concentrations elicited an inhibitory effect in normoglycaemic and diabetic rats. This highlights the NO-glucose uptake mechanism as a possible potential therapeutic target in the treatment of type 2 diabetes.
McGrowder
Donovan
D
Department of Pathology, University of the West Indies, Kingston 7, Jamaica, West Indies. dmcgrowd@yahoo.com
Ragoobirsingh
Dalip
D
Brown
Paul
P
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental; D005260:Female; D005947:Glucose / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D026423:S-Nitroso-N-Acetylpenicillamine / Q000378:metabolism; D026422:S-Nitrosoglutathione / Q000378:metabolism
D001786:Blood Glucose; D007328:Insulin; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D026423:S-Nitroso-N-Acetylpenicillamine; D005947:Glucose