COMPARISON OF THE TIME COURSES OF INSULIN AND THE PORTAL SIGNAL ON HEPATIC GLUCOSE AND GLYCOGEN-METABOLISM IN THE CONSCIOUS DOG

To investigate the temporal response of the liver to insulin and porta l glucose delivery, somatostatin was infused into four groups of 42-h- fasted, conscious dogs (n = 6/group), basal insulin and glucagon were replaced intraportally, and hyperglycemia was created via a peripheral glucose infusion for 90 min (period 1). This was followed by a 240-mi n experimental period (period 2) in which hyperglycemia was matched to period 1 and either no changes were made (CON), a fourfold rise in in sulin was created (INS), a portion of the glucose (22.4 mu mol . kg(-1 ) . min(-1)) was infused via the portal vein (Po), or a fourfold rise in insulin was created in combination with portal glucose infusion (IN SPo). Arterial insulin levels were similar in all groups during period 1 (similar to 45 pM) and were 45 +/- 9, 154 +/- 20, 43 +/- 7, and 128 +/- 14 pM during period 2 in CON, INS, Po, and INSPo, respectively, T he hepatic glucose load was similar between periods and among groups ( similar to 278 mu mol . kg(-1) . min(-1)). Net hepatic glucose output was similar among groups during period 1 similar to 0.1 mu mol . kg(-1 ) . min(-1)) and did not change significantly in CON during period 2. In INS net hepatic glucose uptake (NHGU; mu mol . kg(-1) . min(-1)) wa s -3.8 +/- 3.3 at 15 min of period 2 and did not reach a maximum (-15. 9 +/- 6.6) until 90 min. In contrast, NHGU reached a maximum of - 13.0 +/- 3.7 in Po after only 15 min of period 2, In INSPo, NHGU reached a maximum (-23.6 +/- 3.5) at 60 min, Liver glycogen accumulation during period 2 was 21 +/- 10, 84 +/- 17, 65 +/- 16, and 134 +/- 17 mu mol/g ram in CON, INS, Po, and INSPo, respectively, The increment(period 1 t o period 2) in the active form of liver glycogen synthase was 0.7 +/- 0.4, 6.5 +/- 1.2, 2.8 +/- 1.0, and 8.5 +/- 1.3% in CON, INS, Po, and I NSPo, respectively, Thus, in contrast to insulin, the portal signal ra pidly activates NHGU. In addition, the portal signal, independent of a rise in insulin, can cause glycogen accumulation in the liver.