_-lbstracts of Pap-u 123

with that of glucose. Thus glucose derived from glycogen is oxidized by liver cells to an increased extent. Insulin exerts similar effects and one may suppose that the increase of glucose utilization in thy liver caused by sulphonylurea is mediated by insulin.

414 Insulin Potentiation by Tolbutamide in Eviscerated Animals. J. MADSEN (Denmark).

Eviscerated, nephrrctomized cats were given glucose intravenously at a constant rate in an amount suficient to keep the plasma glucose con- centration nearly constant.

After a control period of 2 hr, one group of these animals was injected intravenously with tolbuta- mide 100 mg/kg - insulin 0.01 unit/kg. A second group received only insulin. A marked (and statistically significant) difference was found be- twern the hypoglycaemic response in the two groups, hypoglycaemia being most pronounced in the first group (25 per crnt compared to 10 per cent in the second group).

\Vhen tolbutamide was given without insulin to glucose-infused, eviscerated cats, a slight, statistic- -

415

ally insignificant effect was found by comparison with a group injected with saline instead of tolbuta- mide. This effect was even more insignificant if the animals had been pancreatectomized 2 days before evisceration.

These results were interpreted as showing a “potentiation“ of insulin by tolbutamide. The effect seen in animals not given insulin is probably due to potentiation of small amounts of endogenous insulin remaining in the animals from before evisceration.

This insulin potentiation might be explained by an action of tolbutamide on the insulin molecule. However, this hypothesis was not sustained by experiments showing that the hypoglycaemic effect of insulin incubated with minute amounts of tolbutamide was not more pronounced than the effect of the same amounts of insulin and tolbuta- mide injected separately.

Changes in Glucose Concentration in the Blood of the Femoral Artery and of the Hepatic, Portal, and Femoral Vein during Onset of Tolbutamide- or Insulin-hypogly- caemia. .4. HASSELBLATT (Germany).

Sulphonylureasy have well-established effects on tissues other than the islets of Langherans, especially on the liver. The possible bearing of such extra- pancreatic actions for the hypoglycaemic response, however, is poorly understood as long as hepatic effects of insulin, liberated into the portal vein and thus reaching the liver directly, are still subject to discussion. In the present experiments, an intra- venous infusion of tolbutamide has been compared to an infusion of insulin into the portal vein. Blood

the femoral artery and the femoral, hepatic, and portal veins using indwelling cannulas. Through- out a two-hour inf&ion of tolbutamide, the reduc- tion in glucose concentration in the hepatic vein exceeded corresponding changes observed in arterial and portal blood. The difference in glucose concentration between femoral artery and femoral vein was scarcely affrcted by tolbutamide. .4p- parently, tolbutamide-hypoglycaemia is primarily achieved by a reduction of hepatic glucose-releasr. r\n infusion of insulin into the portal vein produc?d initially similar changes. During the first 30 min of thr experiment glucose concentration in the hepatic vein was markedly reduced as compared to arterial and portal values. Subsequently, this effect of insulin disappeared and in the second hour of the infusion a steady increase of the glucose gradient between femoral artery and femoral vrin indicated an increased uptake of glucose by the muscular tissues of the hind leg. Insulin-hypogly- caemia is therefore only initially achieved by glucose retension in the liver, while later on glucose utiliza- tion by peripheral tissues is enhanced.

416 Mode of Action of Antidiabetic Drugs. S. OHASHI, S. Tnl;~vc~r and hl. TOBE (Japan).

It was established by us that continuous inf&ion of mesoxalic acid into the pancrratico-duodenal artery results in hypoglycacmia. At the same time. it was demonstrated by means of the rat-hemi- diaphragm mrthod and experiments with hypo- physectomized and adrenalectomized rats that hypoglycaemia brings about an increase of an insulin-like substance in serum.

In hepatectomized dogs under continuous infusion of glucose, sulphonylureacompounds act to product hypoglycarmia, but in pancreatectomizrd and hepato-pancreatectomized dogs, sulphonylurea does not cause a fall in blood sugar level.

In normal dogs, phenethylbiguanide acts to pro- duce hyperglycaemia but not methylbiguanidr. In adrenalectomized dogs administration of bigu- anide compounds did not affect blood sugar level which rcmainrd normal. In hepatectomized dogs under continuous infusion of 250 mg/kg/hr of glucose, it was established by us that the action of biguanide results in hypoglycarmia. It must be noted here that in the actions of biguanide and sulphonylurea differ in that in hepato-pancreatecto- mized dogs administration of biguanide causes fall in blood sugar level.

417 The Effect of Strophanthin G (Ouabain) on the Potential and Short-Circuit Current of the Isolated Skin of Frogs and Toads. 1%‘. F. WIDDAS (United Kingdom).

The potential and short-circuit current of isolated amphibian skins were measured at IO-min intervals before and after the administration of strophanthin G in an apparatus similar to that described by samples have been withdrawn simultaneously from