STUDIES OF THE INSULIN-LIKE ACTIVITY OF SERUM

Abstract

ABSTRACT The influence of the pancreas on the insulin-like activity of serum from dogs and cats was studied under various conditions. In dogs a plastic catheter was inserted into the pancreatic vein, allowing of the determination of blood flow through the catheter and collection of blood samples. After the administration of glucose, an immediate increase in the ILA of serum from the pancreatic vein was observed; the increase in ILA of the serum from the femoral artery was not significant until 10 minutes after the start of the infusion. A smaller, but more sustained increase in ILA of serum from the pancreatic vein was observed after the administration of sulphonurea; subsequent injection of glucose increased the liberation of ILA from the pancreas more than administration of glucose or sulphonurea alone. No change was noted in that part of the ILA of serum, which is unaffected by anti-insulin serum, before and after glucose administration. When pancreatic tissue from rats was incubated in medium containing glucose, a significant liberation of ILA into the medium was observed (as compared with pancreatic tissue incubated without glucose). Lymph, collected from the left thoracic duct of dogs, always contained significantly smaller amounts of ILA than serum. After glucose administration a significant increase in the ILA of lymph and serum was observed. Muscular exercise, produced by electrical stimulation of the hind limbs of intact cats, did not affect the ILA of serum from the femoral vein, as compared with the values obtained from the same vein before stimulation, and estimated by the adipose tissue and the rat diaphragm bioassay. The values of ILA in sera from normal cats were not different from those in sera from normal human subjects. Moreover, the values of ILA in serum protein fractions from normal cats, obtained in starch block electrophoresis with subsequent dialysis against 1 mm CaCl2, corresponded closely to those found in the same fractions from normal human subjects, estimated by the adipose tissue and by the rat diaphragm bioassay. A significant decrease in ILA of serum from pancreatectomized cats was noted 7 days after pancreatectomy. When serum from pancreatectomized cats was fractionated in starch block electrophoresis and treated with a standard procedure of dialysis, and then related to the ILA in the same protein fractions from normal cats, the decrease in ILA in the albumin-alpha-one globulin fraction corresponded to a half-life of 3 days; the decrease in ILA in the alpha-two globulin was in agreement with a half-life of 5 days; moreover the decrease with beta-two-gamma globulin fraction showed a half-life of 6 days. Serum, obtained from cats 4 to 10 days after pancreatectomy, significantly inhibited the activity of added insulin, measured by the adipose tissue as well as by the rat diaphragm bioassay. When serum was obtained from cats more than 10 days after pancreatectomy, the activity of insulin added to the serum was quantitatively recovered. Lipids, like aceto-acetate, free fatty acids or triglycerides, did not interfere with the glucose metabolism of the rat diaphragm or adipose tissue either in the absence or presence of insulin. Ethyl aceto-acetate was incidentally observed to depress markedly the glucose metabolism of the isolated adipose tissue and rat diaphragm and to abolish completely the effect of insulin in these tissues.