No effect of NOS inhibition on skeletal muscle glucose uptake during in situ hindlimb contraction in healthy and diabetic Sprague-Dawley rats.

Nitric oxide (NO) has been shown to be involved in skeletal muscle glucose uptake during contraction/exercise, especially in individuals with Type 2 diabetes (T2D). To examine the potential mechanisms, we examined the effect of local NO synthase (NOS) inhibition on muscle glucose uptake and muscle capillary blood flow during contraction in healthy and T2D rats. T2D was induced in Sprague-Dawley rats using a combined high-fat diet (23% fat wt/wt for 4 wk) and low-dose streptozotocin injections (35 mg/kg). Anesthetized animals had one hindlimb stimulated to contract in situ for 30 min (2 Hz, 0.1 ms, 35 V) with the contralateral hindlimb rested. After 10 min, the NOS inhibitor, N(G)-nitro-l-arginine methyl ester (l-NAME; 5 μM) or saline was continuously infused into the femoral artery of the contracting hindlimb until the end of contraction. Surprisingly, there was no increase in skeletal muscle NOS activity during contraction in either group. Local NOS inhibition had no effect on systemic blood pressure or muscle contraction force, but it did cause a significant attenuation of the increase in femoral artery blood flow in control and T2D rats. However, NOS inhibition did not attenuate the increase in muscle capillary recruitment during contraction in these rats. Muscle glucose uptake during contraction was significantly higher in T2D rats compared with controls but, unlike our previous findings in hooded Wistar rats, NOS inhibition had no effect on glucose uptake during contraction. In conclusion, NOS inhibition did not affect muscle glucose uptake during contraction in control or T2D Sprague-Dawley rats, and this may have been because there was no increase in NOS activity during contraction.

Hong YH ，Betik AC ，Premilovac D ，Dwyer RM ，Keske MA ，Rattigan S ，McConell GK ... -  《-》

Local nitric oxide synthase inhibition reduces skeletal muscle glucose uptake but not capillary blood flow during in situ muscle contraction in rats.

Ross RM ，Wadley GD ，Clark MG ，Rattigan S ，McConell GK ... -  《-》

Local NOS inhibition impairs vascular and metabolic actions of insulin in rat hindleg muscle in vivo.

Bradley EA ，Richards SM ，Keske MA ，Rattigan S ... -  《-》

Inhibiting NOS blocks microvascular recruitment and blunts muscle glucose uptake in response to insulin.

Vincent MA ，Barrett EJ ，Lindner JR ，Clark MG ，Rattigan S ... -  《AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM》

5'-aminoimidazole-4-carboxyamide-ribonucleoside-activated glucose transport is not prevented by nitric oxide synthase inhibition in rat isolated skeletal muscle.

Stephens TJ ，Canny BJ ，Snow RJ ，McConell GK ... -  《CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY》