Hepatic extraction of insulin was examined in anesthetized dogs before and after constant infusion of insulin (20 and 50 mU/min) with use of samples from the portal vein, mesenteric vein, left common hepatic vein, and the femoral artery. In 19 dogs, measurement of portal vein insulin concentration indicated an overall recovery of 110% of the insulin infused. The range varied from 9 to 303%, indicating the potential for serious error in sampling the portal vein. Equilibrium arterial insulin concentrations were achieved 20 min after starting the infusion. Prior to insulin infusion, hepatic extraction of insulin averaged 4.56 plus or minus 0.43 mUmin, representing an extraction coefficient of 0.42 of the insulin presented to the liver. The proportion of insulin extracted by the liver did not change significantly during insulin infusion despite a 10-fold increase in portal vein insulin concentrations. During the infusion of insulin, a significant proportion of the extraheptic clearance of insulin occurred in the mesenteric circulation. Infusion of insulin was associated with a significant increase in insulin extraction by tissues other than the liver and splanchnic beds. Initially, hepatic glucose output average 36 plus or minus 3 mg/min; by 20 min after insulin infusion, it was 16 plus or minus 5 mg/min. Despite continuation of insulin infusion, hepatic glucose output returned to control values even though arterial glucose concentration continued to fall. Hepatic glucose output increased with termination of insulin infusion.

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Abstract.-Hypothalamic extract, containing the releasing factors for anterior pituitary hormones, within minutes stimulated adenyl cyclase activity and adenosine 3' :5'-cyclic phosphate (cyAMP) concentrations in rat anterior pituitary in vitro. Cerebral cortical extract was ineffective and hypothalamic extract had no effect on these parameters in posterior pituitary or thyroid. Prostaglandin E1 also increased adenyl cyclase activity and cyAMP levels in anterior pituitary tissue. Although NaF augmented adenyl cyclase activity, it did not elevate cyAMP. Epinephrine, norepinephrine, histamine, serotonin, dopamine, and vasopressin did not increase either adeny] cyclase or cyAMP. The increased adenyl cyclase and cyAMP produced by hypothalamic extract was associated with greater luteinizing hormone release from anterior pituitary in vitro.Activation of adenyl cyclase and increased levels of adenosine 3':5'-cyclic monophosphate (cyAMP)

Effects of somatostatin (250 ng/kg . min) or saline infusion on hepatic extraction of endogenous and exogenous insulin and glucagon were investigated in anesthetized dogs. After a 20-min control period, somatostatin or saline was infused into the superior mesenteric vein for 100 min. During the final 50 min of the somatostatin or saline infusion, insulin (1.7 mU/kg . min) and glucagon (20 ng/kg . min) were also infused. These infusions were then replaced with a saline infusion for an additional 30 min. Somatostatin rapidly and significantly decreased portal vein insulin and glucagon concentrations. Hepatic extraction of endogenous insulin decreased from the control value of 61 +/- 5% to 29 +/- 10% during the final 20 min of somatostatin infusion before exogenous insulin and glucagon were added to the infusion. The decrease in hepatic extraction of endogenous insulin is based on the mean of the individual values of the eight dogs in the group and may be spurious because of the very low concentrations of insulin which were being measured and the fact that at such low concentrations, some dogs appeared to have negative hepatic extraction of inulin. Glucagon extraction was unchanged (9 +/- 6% compared to 7 +/- 12%) during the first 50 min of infusion of somatostatin. Column chromatography demonstrated that the 3500 mol wt fraction of glucagon comprised 75 +/- 4% of the total glucagon immunoreactivity in the portal vein during the control period and 67 +/- 13% during the infusion of somatostatin. During the final 20 min of somatostatin infusion before the addition of insulin and glucagon, the blood glucose significantly decreased and hepatic glucose output fell from 2.4 +/- 0.4 to 1.4 +/- 0.3 mg/kg . min. However, the insulin to glucagon (3500 mol wt fraction) molar ratio did not change significantly (4.2 +/- 1.1 to 2.6 +/- 0.5). During the final 20 min of the combined infusion of somatostatin, insulin, and glucagon, hepatic extraction of insulin returned to control values and glucagon extraction rose from 7 +/- 12% to 35 +/- 11%. Hepatic glucose output increased without any significant change in the portal vein insulin to glucagon molar ratio. After the termination of the combined infusion, hepatic extraction of insulin was unchanged, but glucagon removal returned to control values. At this time, the portal vein insulin to glucagon ratio rose, and hepatic production of glucose fell below control values. These results demonstrate that somatostatin may influence peripheral insulin and glucagon values by modifying their hepatic extraction and inhibiting their pancreatic secretion. Hepatic glucose output did not always reflect the portal vein insulin to glucagon molar ratio.