Effects of chronic N(omega)-nitro-L-arginine methyl ester administration on glucose tolerance and skeletal muscle glucose transport in the rat.
It has been suggested that nitric oxide (NO) is a key regulator of carbohydrate metabolism in skeletal muscle. The present study was undertaken to examine the effects of chronic in vivo competitive antagonism of NO synthase (NOS) by the administration of N(omega)-nitro-L-arginine methyl ester (L-NAME) in the drinking water (1 mg/ml) for 14 days on glucose tolerance and skeletal muscle glucose transport in rats. Oral glucose tolerance tests (OGTT) revealed an impaired glucose tolerance in the L-NAME-treated rats as reflected by the area under the glucose curve (4675 +/- 514 mg% x 120 min (control) vs 6653 +/- 571 mg% x 120 min (L-NAME treated); P < 0.03). While a large rise in plasma insulin concentration was present in the control rats (0.87 +/- 0.34 ng/ml, P < 0.001) during the first 15 min of the OGTT, rises in plasma insulin concentration were absent in the L-NAME-treated rats (0.18 +/- 0.13 ng/ml, P = NS). Intravenous glucose tolerance tests confirmed an impaired insulin secretion in the L-NAME-treated rats. In contrast, insulin-stimulated 2-deoxyglucose transport was enhanced (P < 0.03) by chronic NOS inhibition (5.29 +/- 0.83 nmol/g/min) compared to control rats (2.21 +/- 0.90 nmol/g/min). Plasma sodium concentrations were lower and plasma potassium concentrations were higher in the L-NAME-treated group, indicating an impaired electrolyte status. We conclude that chronic in vivo administration of a NOS inhibitor, while not impairing basal parameters of carbohydrate metabolism, may manifest different responses than acute exposure to the same agent in vitro.
Balon
T W
TW
Department of Diabetes, Endocrinology and Metabolism, Duarte, California 91010-3000, USA. tbalon@coh.org
Jasman
A P
AP
Young
J C
JC
D000284:Administration, Oral; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D001786:Blood Glucose / Q000032:analysis*; D003847:Deoxyglucose / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D008297:Male; D009124:Muscle Proteins / Q000037:antagonists & inhibitors; D018482:Muscle, Skeletal / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D011188:Potassium / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000097:blood
D001786:Blood Glucose; D004791:Enzyme Inhibitors; D007328:Insulin; D009124:Muscle Proteins; D003847:Deoxyglucose; D012964:Sodium; D019001:Nitric Oxide Synthase; D005947:Glucose; D011188:Potassium; D019331:NG-Nitroarginine Methyl Ester