Effect of Intraportal Calcium Infusion on Insulin and Glucagon Secretion and Hepatic Glucose Output in Anesthetized Dogs*

Abstract

The effects of 2-h intraportal infusion of calcium chloride (8 mg/kg-h) on insulin and glucagon secretion, hepatic extraction of insulin (E1) and glucagon (EGG), and hepatic glucose output (HGO) were studied in six anesthetized mongrel dogs. Since insulin and glucagon have antagonistic effects on HGO, insulin:glucagon molar ratios (I:GG) were also determined in ; portal venous and femoral arterial blood. The calcium infusion increased the portal serum calcium concentration approximately 30% (P < 0.001). The plasma flow in the hepatic artery concomitantly decreased by 40% (P < 0.005). Initially, the insulin secretion into the portal vein was unchanged, but it then fell by 36% (P < 0.01) toward the end of the calcium infusion. In contrast, the secretion of glucagon into the portal vein increased to 48% above the control level (P < 0.05) by the time the calcium infusion was stopped. Neither hepatic extraction of insulin (control value, 66 ± 5%) nor glucagon (control value, 15 ± 11%) showed any significant changes. Portal I:GG, however, fell to a level 57% below the control (P < 0.01) at the end of the calcium infusion, with a somewhat smaller reduction (39%; P < 0.05) of the femoral artery I:GG. Despite the reduction in portal vein I:GG, HGO remained unchanged throughout the entire period of calcium administration. Since neither plasma flows nor insulin or glucagon secretions changed significantly in dogs infused with saline, it is concluded that hypercalcemia per se and not stress factors caused by surgery induced the observed changes in insulin and glucagon secretion. Moreover, the finding of an unchanged HGO in the face of falling portal and peripheral I:GG ratios suggests that hypercalcemia blocks the glucose output from the liver in anesthetized dogs