Effect of a selective rise in hepatic artery insulin on hepatic glucose production in the conscious dog

In the present study we compared the hepatic effects of a selective increas e in hepatic sinusoidal insulin brought about by insulin infusion into the hepatic artery with those resulting from insulin infusion into the portal v ein. A pancreatic clamp was used to control the endocrine pancreas in consc ious overnight-fasted dogs. In the control period, insulin was infused via peripheral vein and the portal vein. After the 40-min,basal period, there w as a 180-min test period during which the peripheral insulin infusion was s topped and an additional 1.2 pmol . kg(-1) . min(-1) of insulin was infused into the hepatic artery(HART, n = 5) or the portal vein (PORT, n = 5, data published previously). In the HART group, the calculated hepatic sinusoida l insulin level increased from 99 +/- 20 (basal) to 165 +/- 21 pmol/l (last 30 min). The calculated hepatic artery insulin concentration rose from 50 +/- 8 (basal) to 289 +/- 19 pmol/l (last 30 min). However, the overall arte rial (50 +/- 8 pmol/l) and portal vein insulin levels (118 +/- 24 pmol/l) d id not change over the course of the experiment. In the PORT group, the cal culated hepatic sinusoidal insulin level increased from 94 +/- 30 (basal) t o 156 +/- 33 pmol/l (last 30 min). The portal insulin rose from 108 +/- 42 (basal) to 192 +/- 42 pmol/l (last 30 min), whereas the overall arterial in sulin (54 +/- 6 pmol/l) was unaltered during the study. In both groups hepa tic sinusoidal glucagon levels remained unchanged, and euglycemia was maint ained by peripheral glucose infusion. In the HART group, net hepatic glucos e output (NHGO) was suppressed from 9.6 +/- 2.1 mu mol . kg(-1) . min-l (ba sal) to 4.6 +/- 1.0 mu mol . kg(-1) . min(-1) (15 min) and eventually fell to 3.5 +/- 0.8 mu mol . kg(-1) . min(-1) (last 30 min, P < 0.05). In the PO RT group, NHGO dropped quickly (P < 0.05) from 10.0 +/- 0.9 (basal) to 7.8 +/- 1.6(15 min) and eventually reached 3.1 +/- 1.1 mu mol . kg(-1) . min(-1 ) (last 30 min). Thus NHGO decreases in response to a selective increase in hepatic sinusoidal insulin, regardless of whether it: comes about because of hyperinsulinemia in the hepatic artery or portal vein.