BASAL HEPATIC GLUCOSE-PRODUCTION IS REGULATED BY THE PORTAL-VEIN INSULIN CONCENTRATION

The ability of portal vein insulin to control hepatic glucose producti on (HGP) is debated. The aim of the present study was to determine, th erefore, if the liver can respond to a selective decrease in portal ve in insulin. Isotopic ([H-3]glucose) and arteriovenous difference metho ds were used to measure HGP in conscious overnight fasted dogs. A panc reatic clamp (somatostatin plus basal portal insulin and glucagon) was used to control the endocrine pancreas. A 40-min control period was f ollowed by a 180-min test period. During the latter, the portal vein i nsulin level was selectively decreased while the arterial insulin leve l was not changed. This was accomplished by stopping the portal insuli n infusion and giving insulin peripherally at half the basal portal ra te (PID, n = 5). In a control group (n = 5), the portal insulin infusi on was not changed and glucose was infused to match the hyperglycemia that occurred in the PID group. A selective decrease of 120 pmol/l in portal vein insulin was achieved (basal, 150 +/- 36 to last 30 min, 30 +/- 12 pmol/l) in the absence of a change in the arterial insulin lev el (basal, 30 +/- 3 to last 30 min, 36 +/- 4 pmol/l). Neither arterial nor portal insulin levels changed in the control group (30 +/- 6 and 126 +/- 30 pmol/l, respectively). In response to the selective decreas e in portal vein insulin, net hepatic glucose output (NHGO) increased significantly, from 8 +/- 1 (basal) to 30 +/- 6 and 14 +/- 2 mu mol.kg (-1).min(-1) by 15 min and the last 30 min (P < 0.05) of the experimen tal period, respectively. Arterial plasma glucose increased from 5.9 /- 0.2 (basal) to 10.5 +/- 0.4 mu mol/l (last 30 min). Three-carbon gl uconeogenic precursor uptake fell from 11.2 +/- 2.9 (basal) to 5.9 +/- 0.7 mu mol.kg(-1).min(-1) (last 30 min), and thus a change in glucone ogenesis could not account for any of the increase in NHGO. With match ed hyperglycemia (basal, 5.5 +/- 0.3 to last 30 min, 10.5 +/- 0.8 mu m ol/l) but no change in insulin, NHGO decreased from 12 +/- 1 (basal) t o 0 (-1 +/- 6 mu mol kg(-1).min(-1), last 30 min, P < 0.05) and hepati c gluconeogenic precursor uptake did not change (basal, 8.0 +/- 1.7 to last 30 min, 8.9 +/- 2.2 mu mol.kg(-1).min(-1)). Thus, the liver resp onds rapidly to a selective decrease in portal vein insulin by markedl y increasing HGP as a result of increased glycogenolysis. These studie s indicate that after an overnight fast, basal HGP (glycogenolysis) is highly sensitive to the hepatic sinusoidal insulin level.