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Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0615
The effect of a
negative arterial-portal venous (a-pv) glucose gradient on
skeletal muscle and whole body nonhepatic glucose uptake was studied in
12 42-h-fasted conscious dogs. Each study consisted of a 110-min
equilibration period, a 30-min baseline period, and two 120-min
hyperglycemic (2-fold basal) periods (either peripheral or intraportal
glucose infusion). Somatostatin was infused along with insulin (3 × basal) and glucagon (basal). Catheters were inserted 17 days
before studies in the external iliac artery and hepatic, portal and
common iliac veins. Blood flow was measured in liver and hindlimb using
Doppler flow probes. The arterial blood glucose, arterial plasma
insulin, arterial plasma glucagon, and hindlimb glucose loads were
similar during peripheral and intraportal glucose infusions. The a-pv
glucose gradient (in mg/dl) was 5 ± 1 during peripheral and
18 ± 3 during intraportal glucose infusion. The net hindlimb
glucose uptakes (in mg/min) were 5.0 ± 1.2, 20.4 ± 4.5, and
14.8 ± 3.2 during baseline, peripheral, and intraportal glucose
infusion periods, respectively (P < 0.01, peripheral vs. intraportal); the hindlimb glucose fractional
extractions (in %) were 2.8 ± 0.4, 4.7 ± 0.8, and 3.9 ± 0.5 during baseline, peripheral, and intraportal glucose infusions,
respectively (P < 0.05, peripheral
vs. intraportal). The net whole body nonhepatic glucose uptakes (in
mg · kg
1 · min1) were 1.6 ± 0.1, 7.9 ± 1.3, and 5.4 ± 1.1 during baseline, peripheral, and
intraportal glucose infusion, respectively
(P < 0.05, peripheral vs.
intraportal). In the liver, net glucose uptake was 70% greater during
intraportal than during peripheral glucose infusion (5.8 ± 0.7 vs.
3.4 ± 0.4 mg · kg1 · min1).
In conclusion, despite comparable glucose loads and insulin levels,
hindlimb and whole body net nonhepatic glucose uptake decreased
significantly during portal venous glucose infusion, suggesting that a
negative a-pv glucose gradient leads to an inhibitory signal in
nonhepatic tissues, among which skeletal muscle appears to be the most
important.
hyperglycemia; arterial-portal venous glucose gradient
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