Effect of perfusion rate on the time course of insulin mediated
skeletal muscle glucose uptake.
Baron, Alain D., Ginger Brechtel-Hook, Ann Johnson, Jessica Cronin,
Rosalind Leaming, and Helmut O. Steinberg.
Department of Medicine, Indiana University Medical Center,
Indianapolis, Indiana 46202 and Richard C. Roudebush Veterans,
Affairs Medical Center, Indianapolis, Indiana 46202
APStracts 3:0181E, 1996.
To better define the time course of skeletal muscle glucose uptake and
its modulation by changes in perfusion, we performed systemic
euglycemic hyperinsulinemic clamps (40 mU/m2/min) for a 90 minute
period in a group of lean, insulin sensitive subjects (n=9) on two
occasions (4 weeks apart) with insulin mediated vasodilation intact
or inhibited. Insulin mediated vasodilation was inhibited by an
intrafemoral artery infusion of L-NMMA, a specific inhibitor of
nitric oxide synthase. During the study, leg blood flow (LBF) and
arteriovenous glucose difference (AVG_) were measured every 10
minutes, leg glucose uptake (LGU) was calculated as LGU=LBF*AVG_. The
systemic insulin infusion caused a time dependent increase in LBF
from 0.194+/-0.024 to 0.349+/-0.046 L/min (p<0.01). The
intrafemoral artery infusion of L-NMMA completely inhibited this
increase in LBF. AVG_, LGU and whole body glucose disposal rates
increased in a time dependent manner in both studies. The maximum
AVG_ was lower with insulin mediated vasodilation intact than
inhibited (25.9+/-2.5 vs 35.0+/-1.6 mg/dl, p<0.001). The time to
achieve half maximal (T1/2) AVG_ was somewhat longer with insulin
mediated vasodilation intact compared to inhibited (35.6+/-4.1 vs
29.7+/-1.6 min, p<0.01). Maximal LGU was 93.9+/-26.8 and 57.2+/
-11.6 mg/min (p<0.005), and the T1/2 LGU was 50.2+/-16.0 and
36.3+/-8.8 min (p=0.1) during intact and inhibited insulin mediated
vasodilation respectively. Thus, insulin mediated vasodilation has a
modest effect to slow the time course at which insulin stimulates
glucose uptake but has a marked effect to augment the maximal rate of
insulin stimulated glucose uptake in skeletal muscle. Impaired
insulin mediated vasodilation as observed in patients with essential
hypertension may explain at least in part the insulin resistance
observed in these patients.
Received 13 March 1996; accepted in final form 12 August 1996.
APS Manuscript Number E124-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 19 September 1996