Shirley Weisenfeld

Adsorption of Insulin to Infusion Bottles and Tubing

The adsorption of clinically used quantities of insulin to infusion systems was studied. Isotonic saline solutions containing tracer quantities of beef insulin-I-131, with or without varying amounts of nonradioiodinated (carrier) regular beef insulin, were added to bottles of 500 ml. infusion sets. The solutions were then allowed to flow out into collection beakers. Adsorption was assessed by measuring the decrease of radioactivity in the solutions and/or recovery from the bottles by 30 per cent potassium hydroxide (KOH). The influence of human serum albumin (HSA) on adsorption was evaluated by repeating the experiments after HSA was added to the infusion fluid. Adsorption of insulin-I-131 to both bottles and tubing was considerable, especially at low concentrations of carrier insulin. HSA effectively reduced the adsorption to clinically insignificant amounts.

Utilization of glucose in normal and diabetic rabbits; effects of insulin, glucagon and glucose.

In the fasting state the concentration of glucose in blood and extracellular tissues is determined by the balance between the rate of glucose removal by tissue cells and the rate of glucose supply, primarily from liver. The effect of any hypoglycemic agent must therefore be due to an acceleration of glucose removal, a diminution in the rate of supply, or some combination of both. In the intact animal, these two actions are not readily distinguishable if observations are restricted to changes in the blood sugar concentration alone. However, if the blood glucose is labeled with glucose-C, such distinction becomes possible so long as the sources of newly formed glucose remain unlabeled or labeled to an insignificantly small extent. The chief purpose of the present study has been to assess, with the aid of glucose-C, the relative importance of reduction in glucose supply and increase in glucose utilization in the hypoglycemia induced by insulin. An attempt has been made to evaluate the effects of insulin (a) administered exogenously by subcutaneous and intravenous routes, and (b) secreted endogenously in response to hyperglycemia produced by intravenous glucose or glucagon administration. It has been of further interest to attempt to determine whether insulin is secreted endogenously in response to the administration of certain other sugars and to apply the same methods to the evaluation of the endogenous insulin-secretory response to glucose following a period of insulin therapy.

Effect of 17-ethyl-19-nortestosterone on hyperglycemic action of glucagon in humans.

Summary Sixteen patients were studied as to the effect of Nilevar on hyperglycemic response to glucagon. Nilevar abolished or profoundly diminished this response. This effect was reversible when Nilevar therapy was stopped. Nilevar had no apparent effect on the control of 3 diabetic patients nor on the 24-hour thyroid I131 uptakes of 8 patients. Possible mechanisms are discussed.

Failure of 17α-Ethyl-19-Nortestosterone to Effect Plasma 17-Hydroxycorticosteroids and ACTH Responsiveness in Man.

Conclusions In 5 subjects receiving clinically effective oral doses of Nilevar, there was no alteration in adrenocortical function as measured by plasma 17-OHCS levels before and after intravenous ACTH.

Inactivation of insulin by the isolated liver of the bullfrog.

Experiments are presented in which insulin solutions were perfused through isolated frog livers in order to study the inactivation of this hormone by liver tissue. The solutions were recirculated many times and aliquots were tested biologically at various intervals for hypoglycemic activity. While insulin retains its activity after a single frog liver perfusion, it is gradually inactivated with increasing numbers of reperfusions. This result is in accord with the inactivation of insulin by liver slices and liver brei as reported by others. The relatively slow inactivation of insulin when perfused through the isolated frog liver is in contrast to the inactivation of glucagon which, as previously reported, loses its hyperglycemic activity after a single perfusion through this preparation. The general significance of this finding is discussed.

Studies of the mechanism of action of sulfonylurea derivatives.

and the other a young girl with juvenile, unstable diabetes of recent onset. The hypoglycemic capacity of the drug varied among the patients studied. The most striking response was obtained in the young patient. In the other two patients the responses were mild to moderate. 2. The lowering of blood and urinary sugar by carbutamide was not associated with any consistent changes in the number of circulating eosinophiles or the urinary excretion of reducing corticosteroids. Carbutamide did not appear to have any direct effect on nitrogen, sodium, potassium or water balances, or body weight. In one patient the administration of carbutamide was associated with retention of inorganic phosphorus. 3. The repeated administration of glucagon for several days produced more or less sharp, sustained rises in blood and urinary sugar and a fall in serum inorganic phosphorus. In the unstable patient, the hyperglycemia and glycosuria induced by glucagon was associated with negative nitrogen balance. Effect of glucagon on nitrogen balance was also seen in lesser degree in one of the stable patients. These results are in agreement with other studies on glucagon in our laboratory and will be reported later. 4. The blood sugar lowering effect of carbutamide could be quantitatively antagonized or counterbalanced by the administration of glucagon. Conversely, the blood sugar raising effect of glucagon could be quantitatively antagonized or counterbalanced by the administration of carbutamide. The capacity of glucagon to raise the blood sugar appeared to be diminished to a greater or less degree in the presence of carbutamide in the two patients in whom this effect was investigated. Inhibition was noncompetitive. This inhibitory effect of carbutamide appeared to be directly proportional to its blood sugar lowering capacity. While carbutamide markedly decreased the hyperglycemic and glycosuric response to glucagon in the unstable patient, it did not proportionately diminish the effects of glucagon on nitrogen balance and serum inorganic phosphorus. 5. In the patient with unstable diabetes carbutamide produced not only a marked lowering but a stabilization of the blood sugar levels. This stabilizing effect was also reflected in the levels of plasma inorganic phosphorus, sodium balance and N A : K ratio.