EFFECT OF A SELECTIVE RISE IN SINUSOIDAL NOREPINEPHRINE ON HGP IS DUETO AN INCREASE IN GLYCOGENOLYSIS

To determine the effect of a selective rise in liver sinusoidal norepi nephrine (NE) on hepatic glucose production (HGP), norepinephrine (50 ng . kg(-1) . min(-1)) was infused intraportally (Po-NE) for 3 h into five 18-h-fasted conscious dogs with a pancreatic clamp. In the contro l protocol, NE (0.2 ng . kg(-1) . min(-1)) and glucose were infused pe ripherally to match the arterial NE and blood glucose levels in the Po -NE group. Hepatic sinusoidal NE levels rose similar to 30-fold in the Po-NE group but did not change in the control group. The arterial NE levels did not change significantly in either group. During the portal NE infusion, HGP increased from 1.9 +/- 0.2 to 3.5 +/- 0.4 mg . kg(-1 ) . min(-1) (15 min; P < 0.05) and then gradually fell to 2.4 +/- 0.4 mg . kg(-1) . min(-1) by 3 h. HGP in the control group did not change (2.0 +/- 0.2 to 2.0 +/- 0.2 mg . kg(-1) . min(-1)) for 15 min but then gradually fell to 1.1 +/- 0.2 mg . kg(-1) . min(-1) by the end of the study. Because the fall in HGP from 15 min on was parallel in the two groups, the effect of NE on HGP (the difference between HGP in the tw o groups) did not decline over time. Gluconeogenesis did not change si gnificantly in either group. In conclusion, elevation in hepatic sinus oidal NE significantly increases HGP by selectively stimulating glycog enolysis. Compared with the previously determined effects of epinephri ne or glucagon on HGP, the effect of NE is, on a molar basis, less pot ent but nore sustained over time.