Effect of hyperglycemia on hepatic extraction of insulin in totally pancreatectomized dogs.

Using the glucose clamp technique, we investigated the effect of blood glucose levels on hepatic extraction of insulin in pancreatectomized dogs. A primed continuous infusion of regular insulin was administered at a rate 1.5 mU/kg body wt./min into the portal or peripheral vein and the blood glucose level was clamped at hyperglycemia (over 200 mg/dl) or euglycemia (below 100 mg/dl) by a variable infusion of glucose through the saphenous or portal vein. Plasma insulin concentrations were measured during portal or peripheral insulin infusion, as were the metabolic clearance rates of insulin during insulin infusion via each route. Hepatic extraction of insulin was calculated from the two metabolic clearance rates using the insulin kinetic model (Pilo' method). Hepatic extraction of insulin during the hyperglycemic clamp was 45.8 +/- 2.5%, significantly higher than that during the euglycemic clamp (35.7 +/- 2.8%: p less than 0.01). When glucose was infused into the portal instead of the peripheral vein during the euglycemic clamp, hepatic extraction of insulin increased (44.7 +/- 3.4 vs 37.6 +/- 2.9%: p less than 0.05). It was concluded that hyperglycemia increases the hepatic extraction of insulin. Moreover, portal hyperglycemia during the euglycemic clamp also increases the hepatic extraction of insulin. It is suggested that portal glucose concentration may affect the hepatic extraction of insulin.