Comparison of the time courses of insulin and the portal signal on hepatic glucose and glycogen metabolism in the conscious dog.

Abstract

To investigate the temporal response of the liver to insulin and portal 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-min experimental period (period 2) in which hyperglycemia was matched to period 1 and either no changes were made (CON), a fourfold rise in insulin was created (INS), a portion of the glucose (22.4 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 (INSPo). Arterial insulin levels were similar in all groups during period 1 ( 45 pM) and were 45 9, 154 20, 43 7, and 128 14 pM during period 2 in CON, INS, Po, and INSPo, respectively. The hepatic glucose load was similar between periods and among groups ( 278 mol kg 1 min 1 ). Net hepatic glucose output was similar among groups during period 1 ( 0.1 mol kg 1 min 1 ) and did not change significantly in CON during period 2. In INS net hepatic glucose uptake (NHGU; mol kg 1 min 1 ) was 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 mol/gram in CON, INS, Po, and INSPo, respectively. The increment (period 1 to 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 INSPo, respectively. Thus, in contrast to insulin, the portal signal rapidly activates NHGU. In addition, the portal signal, independent of a rise in insulin, can cause glycogen accumulation in the liver. (