The hepatic glucose response to insulin in the un-anesthetized dog.

The precise action of insulin on the liver remains open to investigation and understanding despite considerable data which have been accumulated. Dunn et al. (1) with the use of CYlabeled glucose in the dog, express one point of view when they state: “These isotope tracer studies, which clearly indicate an action of insulin in inhibiting glucose output, may be added to a growing body of information which is making it increasingly obvious that a major action of insulin is exerted on the liver.” These writers add that their observations ‘L. . . extend these earlier findings by demonstrating that insulin does in fact act immediately to inhibit glucose production by liver.” In liver slices of diabetic rats glucose uptake is subnormal and glucose output is excessive. As measured in this system, Renold et al. (2) found that the diabetic lesion is not immediately corrected by the addition of insulin, but requires several hours to several days. Haft and Miller (3) perfusing the isolated rat liver with a medium containing 350 mg. of glucose per 100 ml., found this value rising to 600 mg. in 1 hour, unaffected by insulin. In the alloxan diabetic rat liver insulin produced an increased removal of glucose from the medium between 1.5 and 4.0 hours of perfusion at these glucose concentrations (3). No such effect has been demonstrable in the cat or rabbit liver (4) even though fatty acid synthesis (5), peptide synthesis (6), and incorporation of Cl4 labeled glucose into glycogen (7) can be stimulated by the addition of insulin to liver slices in vitro under certain conditions. Studies in vivo on hepatic metabolism in the diabetic dog have shown an increased hepatic glucose production (8). There is also reported an increased splanchnic glucose output in poorly controlled human diabetics compared with the normal subject (9). The splanchnic glucose output in normal man decreases after insulin administration (Bondy et al. (10)). This observation has been confirmed by Sherlock et al. (11) with the conclusion that insulin produces an hepatic as well as peripheral uptake of glucose. On the other hand, measurement of portal-hepatic venous glucose concentrations shows no change in the hepatic glucose gradient after insulin is given to normal unanesthetized dogs (Ashmore et al. (12)). The present study is undertaken to