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Am J Physiol Endocrinol Metab 278: E544-E552, 2000;
0193-1849/00 $5.00
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Vol. 278, Issue 3, E544-E552, March 2000

Combined intraportal infusion of acetylcholine and adrenergic blockers augments net hepatic glucose uptake

Masakazu Shiota, Patricia Jackson, Pietro Galassetti, Melanie Scott, Doss W. Neal, and Alan D. Cherrington

Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0615

Portal glucose delivery in the conscious dog augments net hepatic glucose uptake (NHGU). To investigate the possible role of altered autonomic nervous activity in the effect of portal glucose delivery, the effects of adrenergic blockade and acetylcholine (ACh) on hepatic glucose metabolism were examined in 42-h-fasted conscious dogs. Each study consisted of an equilibration (-120 to -20 min), a control (-20 to 0 min), and a hyperglycemic-hyperinsulinemic period (0 to 300 min). During the last period, somatostatin (0.8 µg · kg-1 · min-1) was infused along with intraportal insulin (1.2 mU · kg-1 · min-1) and glucagon (0.5 ng · kg-1 · min-1). Hepatic sinusoidal insulin was four times basal (73 ± 7 µU/ml) and glucagon was basal (55 ± 7 pg/ml). Glucose was infused peripherally (0-300 min) to create hyperglycemia (220 mg/dl). In test protocol, phentolamine and propranolol were infused intraportally at 0.2 µg and 0.1 µg · kg-1 · min-1 from 120 min on. ACh was infused intraportally at 3 µg · kg-1 · min-1 from 210 min on. In control protocol, saline was given in place of the blockers and ACh. Hyperglycemia-hyperinsulinemia switched the net hepatic glucose balance (mg · kg-1 · min-1) from output (2.1 ± 0.3 and 1.1 ± 0.2) to uptake (2.8 ± 0.9 and 2.6 ± 0.6) and lactate balance (µmol · kg-1 · min-1) from uptake (7.5 ± 2.2 and 6.7 ± 1.6) to output (3.7 ± 2.6 and 3.9 ± 1.6) by 120 min in the control and test protocols, respectively. Therefter, in the control protocol, NHGU tended to increase slightly (3.0 ± 0.6 mg · kg-1 · min-1 by 300 min). In the test protocol, adrenergic blockade did not alter NHGU, but ACh infusion increased it to 4.4 ± 0.6 and 4.6 ± 0.6 mg · kg-1 · min-1 by 220 and 300 min, respectively. These data are consistent with the hypothesis that alterations in nerve activity contribute to the increase in NHGU seen after portal glucose delivery.

hepatic blood flow; lactate


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